Projects

Abstract

Mycobacterium abscessus (Mab) is a nontuberculous mycobacterium (NTM) that causes opportunistic infections in patients with chronic lung diseases, like cystic fibrosis and chronic obstructive pulmonary disease and its incidence in disease is increasing. Infections with Mab are notoriously difficult to treat as it demonstrates a high resistance to antibiotics and the correlation between the in vitro susceptibility of Mab isolates and the clinical outcome is limited. For Mab lung diseases, the role of antibiotic tolerant persisters in disease and treatment has not been established. However, given the chronic nature of the disease, as well as the long duration of treatment and the frequent occurrence of relapses, we hypothesize that antibiotic tolerant persister formation is of great importance. Combining the multidisciplinary expertise of LMPH (UA) and the BREATHE/Microbiology lab (UZ/KUL) this project will provide fundamental knowledge about Mab antibiotic persistence such as i) levels of persister formation in different Mab clinical isolates under clinically relevant conditions for various antibiotic classes; ii) the mechanism behind antibiotic induced persister formation and iii) its importance in disease progression and treatment outcome. We strongly believe a thorough understanding of the mechanisms involved in persister formation will aid in the identification of potential new drug targets that can act on persistent Mab ultimately leading to improved treatment options.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Flaviviruses are a growing threat in Europe, where West Nile virus (WNV), Tick-borne encephalitis (TBEV), and Usutu virus (USUV) co-circulate. Human travel can also introduce other flaviviruses, like Japanese encephalitis virus (JEV). New diagnostic and preventive methods are needed to reduce the risk of epidemics from these neurotropic viruses with sometimes serious medical consequences. NS1 is a potential target for diagnosis and prevention. It can be detected in the blood before symptoms, making it a promising biomarker for antigen-capture assays. However, these assays suffer from low specificity due to cross-reactivity. NS1 vaccination and passive transfer of anti-NS1 monoclonal antibodies protect mice from flavivirus infection. However, little is known about NS1 epitopes responsive to protection. My project aims to evaluate the potential of NS1 in flavivirus diagnosis and prevention. I will develop a unique set of highly specific monoclonal antibodies, which will be tested and validated for novel diagnostic applications and for finding protective epitopes for an NS1-subunit vaccine. This project can improve the monitoring, prevention, and management of flavivirus infections, reducing their impact on human health and welfare.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Ceconi Martina

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The Respiratory Syncytial Virus (RSV) is, globally, a prominent cause of acute lower respiratory tract infections (ALRTI) in both infants and the elderly. Recently, two vaccines and one monoclonal antibody (mAb) have been developed and approved for use in these populations. It is expected that the new mAb (Nirsevimab) will be widely administered to children under two years old in the upcoming RSV seasons. The extensive use of this prophylactic could induce unexpected changes in RSV infection and resistance mechanisms, as observed on a smaller scale worldwide with the use of the older and widely used mAb, palivizumab. Therefore, it is crucial to comprehend the evolution of RSV and predict potential mutations that may occur under the selective pressure exerted by these mAbs, posing a real threat to the efficacy of available preventive measures. Hence, the comprehensive approach presented in this project will enhance our understanding of how prophylactic measures may influence RSV evolution, providing valuable insights for public health strategies and preparedness against emerging RSV strains.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Van Hoorenbeeck Kim
• Fellow: Serrano Cano Francisco Ivan

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Mycobacterium abscessus (Mab) is an increasingly emerging human pathogen responsible for a wide spectrum of diseases, including chronic pulmonary and skin infections. The treatment of Mab infections is a great challenge as it demonstrates a high resistance to antibiotics and the correlation between the in vitro susceptibility of Mab isolates and the clinical outcome is limited. For Mab lung diseases, the role of persisters in disease and treatment has not been established. However, given the chronic nature of the disease, as well as the long duration of treatment and the frequent occurrence of relapses, we hypothesize that persister formation could be of importance here. This project aims to increase fundamental knowledge about Mab persistence, such as frequency of persister formation for various antibiotic classes in different Mab isolates under standard and clinically relevant culture conditions and the molecular mechanisms involved in persister formation. Since Mab can replicate in macrophages, Mab persister levels in an intracellular environment will also be determined. We strongly believe a thorough understanding of the mechanisms involved in persister formation will aid in the identification of potential new drug targets that can act on persistent Mab ultimately leading to improved treatment options.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Geerts Lisa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Respiratory Syncytial Virus (RSV) is a significant cause of respiratory tract infections, particularly affecting young children and the elderly. Why RSV results in asymptomatic or mild infections in some, and life-threatening bronchiolitis in others, remains poorly understood. Severe disease is thought to result from both direct viral damage and excessive immune activation and inflammation. RSV is able to modulate the immediate responses in infected cells, by evading innate antiviral immunity and interfering with cell death pathways that are activated to counteract infection. Currently, the knowledge on how RSV interferes with these protective responses upon infection, and how this might contribute to exaggerated disease is scattered. Most studies use lab strains, potentially lacking key evasion mechanisms and not representing currently circulating strains. It's not yet known if and how virus variability might lead to different immediate cellular responses upon infection, and if this could, at least partially, explain differences in RSV disease severity. This project aims to comprehensively investigate early responses to RSV infection, focusing on innate immunity and cell death pathways, by using a unique library of bona-fide clinical isolates and relevant hAEC cultures. Validation of the results will be done using RSV reverse genetics, and the translational value will be confirmed in a set of >100 nasal samples from RSV-infected infants with different disease severity.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Wullaert Andy
• Fellow: Fransen Axelle

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Leishmania parasites are transmitted via the bite of infected female sand flies. Inside this vector, parasites have to overcome different hurdles before they can differentiate into their metacyclic, infective form, during a process which is called metacyclogenesis. This PhD project will focus on the identification of Leishmania infantum genes that can influence the development and metacyclogenesis of parasites in the vector and hereby impact successful transmission from sand fly to vertebrate host. As both up- and downregulation of certain genes may result in enhanced transmission, two different methodologies will be applied to identify potential transmission-related genes, both in collaboration with prof. dr. Ouellette (Quebec, Canada). On the one hand, repeated infection of sand flies with an already established Leishmania COSMID library will allow for selection of more transmissible parasites that harbor those specific COSMIDs containing genes providing a benefit in the vector. Genes responsible for these observed gain-of-functions in the sand fly will be unveiled using COSMID sequencing. On the other hand, loss-of-function will be explored in parallel using a similar approach for a recently developed Leishmania CRISPR-Cas9 library. Ultimately, the identification of genes involved in transmission not only will provide useful insights on the transmission process, but it might also open doors for the development of novel transmission-blocking strategies in the future.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Hendrickx Sarah
• Fellow: Van den Broeck Lauren

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

African trypanosomiasis is a tsetse fly transmitted disease indigenous for the African continent. Millions of people in 36 sub-Saharan African countries are currently at risk of this fatal infection. The current drugs are faced with limitations of toxicity and drug resistance and to date not a single effective vaccine is available. For both vaccine development and elimination endeavours, an adequate understanding of the immunology of infection onset, disease progression and distribution of parasites to tissue sanctuary niches is crucial. Our recent work has identified the skin and lungs as overlooked tissue reservoirs. Immunological studies in mouse models unveiled the increased presence of γδ T cells in infected tissues and a profound importance of these cells in regulating parasite control and host survival. The current research initiative will investigate the complex dynamics of γδ T cells during Trypanosoma brucei infections. The project consists of three distinct work packages (WP1-3). WP1 focuses on characterizing tissue-specific γδ T cell subsets following a natural, tsetse fly-transmitted T. brucei infection, focussing on their tissue tropism and contribution to immune cell recruitment and pathology. WP2 aims to explore the molecular mechanisms underlying the immune response of γδ T cells against T. brucei parasites, including their interaction with the major variant-specific surface glycoprotein (VSG) of the parasite. In vitro studies will inform about the responsiveness and functional importance of gene expression patterns of γδ T cells to parasitic stimulation. WP3 investigates the role of γδ T cells in the development of antiparasitic adaptive immunity and post-treatment tissue repair. This research employs advanced techniques such as single-cell transcriptomics, multiparameter immunoprofiling, and histopathological examinations in unique infection models to unravel the intricate interplay between γδ T cells and T. brucei, offering unprecedented basic scientific insights and revealing opportunities for immunotherapeutic interventions against trypanosomiasis.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Baeza Garcia Alvaro
• Fellow: Jacobs Yentl

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In the last decade, stem cells have been discovered to serve as a reservoir for many pathogenic organisms. Our recent research on visceral leishmaniasis (VL) revealed that hematopoietic stem cells (HSC) in the bone marrow underlie treatment failure and relapse. These cells exhibit a unique transcriptional signature (StemLeish) and provide an environment for the development of parasite quiescence, a metabolic state that is impervious to drug treatment. This project will build upon these cutting-edge findings in order to obtain (i) a thorough characterization of immunological processes in the HSC niche that are at the basis of treatment failure, and (ii) mechanistic insights in the possible trigger(s) of VL relapse and the particular role of Macrophage Migration Inhibitory Factor (MIF). From an applied research viewpoint, this project will (iii) establish the diagnostic value of HSC biomarkers using patient samples and (iv) install a novel drug screening platform based on the developed tools to predict and capture the risk of relapse. It is expected that this project will open new therapeutic avenues that may extend beyond leishmaniasis and be revolutionary in the precarious battle against treatment failure.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Baeza Garcia Alvaro
• Fellow: Dirkx Laura

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The inability to acquire protective immunity against Plasmodium parasite infections is a significant obstacle to malaria control. Previous research has shown that Plasmodium parasites use an active mechanism to control the host immune response by expressing a molecule called PMIF, which is similar to the host macrophage migration inhibitory factor. Mutant parasites that lack PMIF have been shown to inhibit both cellular and humoral immune responses. However, the precise way in which parasite PMIF inhibits host MIF and host immune responses is not yet fully understood. This project aims to investigate the complex interplay between host and parasite-derived MIF molecules and their impact on the acquisition of protective immunity, as well as improving current and future therapeutic interventions. To achieve this, the following specific aims will be pursued: 1) Understanding the molecular basis of pro-inflammatory activation of T cell responses by host MIF and PMIF, 2) Determining the contribution of MIF molecules to the induction of Plasmodium antigen recognition and recall responses during liver and blood infection, and 3) Examining the impact of MIF functional polymorphism on the acquisition of sterile immunity against malaria. 1246

Researcher(s)

• Promoter: Baeza Garcia Alvaro
• Fellow: Bemelmans Britt

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

With this project, we will establish a Respiratory Virus Repository at the University of Antwerp. The collection of respiratory viruses will be available to companies, academic groups, and research institutions.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: De Winter Benedicte
• Co-promoter: Van Hoorenbeeck Kim
• Co-promoter: Verhulst Stijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Despite the concept that infectious diseases are usually caused by a single pathogen, in reality, we are constantly challenged by multiple pathogens and growing evidence indicates that co-infections are a much more common event than clinically perceived. The respiratory tract is the first point of contact with airborne pathogens and the most common site for infections. Hence, human respiratory infections contribute to substantial morbidity and economic losses worldwide, resulting in approximately 2.5 million deaths each year. Recent findings have shed light on a crucial factor in the severity of respiratory infections: the role of co-infections. Considering the public health importance of respiratory infections and the scarcity of research on the impact of co-infections in the balance of immune defences, this project proposes to study the in vitro and in vivo effects of diverse parasitic, viral, and bacterial co-infections on different types of immune cellsin the lungs, and comprehensively characterize tissue local microenvironment and host-pathogen interactions. Additionally, we will investigate the immunomodulatory effects of protozoan infections on vaccines and chemotherapy treatments and their impact on the protection against targeted pathogens. Objectives include: elucidate the molecular mechanisms underlying immunological responses in the lungs and the susceptibility to co-infections; investigate altered immune responses of vaccines and the changes in the response to co-infection after chemotherapy of the primary infection. In the end, this study will allow deeper understanding of respiratory co infections that could pave the way for the development of improved diagnostic and prognostic techniques, as well as the potential for proposing supportive treatments and vaccines. Notwithstanding, the development of this project will open up new avenues for future co infection research and propel the fellow towards establishment as a successful independent researcher.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter
• Fellow: Araujo Sergio

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

During the COVID-19 pandemic, detection of Sars-CoV-2 in wastewater has reinforced the strength of wastewater-based epidemiology to monitor outbreaks and to deliver complementary data to guide and evaluate socio-economic policy strategies. Wastewater indeed contains a wealth of information on types of pathogens circulating in humans. This unique virome and microbiome window has not yet been sufficiently exploited for its many benefits. With advances in molecular methods available today, we can map the virome and antimicrobial resistance genes of populations through wastewater surveillance, and optimize monitoring of the next global challenges linked to pathogens. Optimization of methods for wastewater collection, for pre-treatment of wastewater and for nucleic acid purification will be optimized during this Phd for a selection of pathogens, including SARS-CoV-2 and other respiratory viruses. In addition, detection methods will be developed for other pathogens such as Adenoviruses, Enteroviruses, Hepatitis E virus and Norovirus, and for a selection of AMR genes. Finally, sampling and wastewater processing methods will be optimized for use in rural and low resource settings.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Ul Hudda Noor

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This BOF-SRG project aims to support my independent research line, exploring host-pathogen interactions and unraveling pathophysiological mechanisms involved in the intracellular invasion of the olfactory network by understudied neurotropic infectious agents of various aetiologies, that have been found to infect the upper respiratory tract and cause neuropathological manifestations. Currently, as a senior postdoc at the Laboratory of Microbiology, Parasitology, and Hygiene (LMPH), I am leveraging my extensive experience on Hansen's Disease (HD) to investigate the causative pathogen of HD, Mycobacterium leprae. My research in the field of HD has been internationally recognized, and I have published four first-author papers on HD, including two fundamental studies that have shifted the paradigm on the infection mechanism: one unveiling asymptomatic carriage of bacilli in the nose with a potential role in the chain of transmission; and the other on the aerial route as the predominant mode of infection and transmission. The evidence of nasal mucosa infection and high incidence of olfactory dysfunction in HD, as well as the knowledge gap regarding the cellular mechanisms of infection, warrant further investigation. My hypothesis is that M. leprae can infect olfactory ensheathing cells (OECs) and this unexplored niche can be an undisclosed route for the initial invasion of nerve tissues, play a role in immune evasion, and contribute to the colonization of nasal mucosa and the persistence of chronic infection. The development of this project will increase our understanding of this debilitating disease and shed light on the unknown mechanisms by which it can evade immune responses, colonize nerve tissues, and develop chronic disease. It will also provide the cornerstone for establishing an international partnership with research groups in the Global South (Brazil) working on HD and other neglected tropical diseases (NTDs). In the short term, I also plan to explore the infection of OECs by other neurotropic parasitic, viral, and bacterial pathogens under investigation at LMPH, such as Leishmania, RSV, and Streptococcus, which can also invade and damage the PNS and/or use the olfactory pathway as a route of entry into the CNS. In the middle term, I envisage investigating co-infections with pathogens of different aetiologies in the established infection model of OECs. In the long term and beyond infectious diseases, this project will open opportunities for collaboration on regenerative medicine studies, as the use of OECs is also a promising strategy for neuroprotection and the regeneration of neural tissues.

Researcher(s)

• Promoter: Araujo Sergio

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In his research plan for the next five years, the researcher focuses on the following questions. He wants to define the molecular basis of proinflammatory activation of immune responses by host and PMIF. In addition, he wants to investigate the physiological relevance of MIF-driven modulation of T cell function in advanced malaria. Finally, the researchers aims to improve current therapeutic approaches targeting binding of CD74-MIF by pharmacological or vaccine approaches. The proposal combines the modulation of immune responses by MIF and T cell biology immunology to improve current knowledge and development of parasitic diseases. Although this project focuses on malaria the knowledge gained will also be extrapolable to other parasites that express a MIF orthologue, such as Leishmania.

Researcher(s)

• Promoter: Baeza Garcia Alvaro
• Fellow: Baeza Garcia Alvaro

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Major knowledge gaps exist in the frequent treatment failures during visceral leishmaniasis (VL). Our cutting-edge research has identified the bone marrow as a sanctuary tissue where parasites survive treatment. Combination of large-scale drug screening and immunophenotyping identified stem cells as highly susceptible host cells. These cells exhibit the transcriptional "StemLeish" program and provide an environment for the development of parasite quiescence, a metabolic state that is impervious to drug treatment. Our recently completed genome-wide transcriptomics studies provide unprecedented insights in quiescence and lead to the identification of various potential drivers of entry into a dormant state. Based on the collective multidisciplinary expertise of LMPH (UA) and CMIM (VUB-VIB), this project will provide detailed information about the host- and parasite-related factors underlying relapse by (i) obtaining fundamental compositional, functional, single cell and spatial insights in the immunopathology of bone marrow infection, (ii) deciphering the role of Stemleish genes in infection and in stimulation of parasite quiescence (iii) identifying parasite driver genes that trigger the development of quiescence and (iv) explore the therapeutic impact of pharmacological inhibition of major Stemleish gene products and related pathways. It is expected that in-depth molecular understanding of the stem cell niche and parasite quiescence will be revolutionary for VL treatment.

Researcher(s)

• Promoter: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

We have described a mechanism by which the Plasmodium expressed cytokine Macrophage Migration inhibitory Factor (PMIF) acts to prevent the acquisition of immunologic memory by activating the host MIF receptor CD74 to establish severe malaria and parasite replication. Immunoneutralization or genetic deletion of PMIF, strictly conserved in all Plasmodium species, improves malaria immunologic memory, reduces parasite burden, and protects from severe malaria. Moreover, we have shown in genetic PMIF deficiency experiments that malaria protection and development can be recapitulated with a small-molecule antagonist developed by our group. This novel molecule, called 26k, was identified by leveraging the unique features of PMIF structural biology. It specifically blocks PMIF interaction with its host receptor CD74, inhibiting parasite replication in the host liver and protecting from severe malaria. We hypothesize that such a PMIF inhibitor provides a unique approach for interfering with a parasite-specific mechanism for suppressing host immunity and offers a new tool for combating Plasmodium infection. This project aims to identify better quality and pharmacologically tractable PMIF antagonists for lead optimization programs and will provide a proof-of-concept that PMIF pharmacological inhibition increases memory immunity to Plasmodium infection. We will accomplish our objective by pursuing the following Specific Aims: Aim 1: Identification and optimization of novel PMIF inhibitors. Aim 2: Evaluation of lead PMIF inhibitors in experimental models of Plasmodium infection. Aim 3: Evaluation of the full therapeutic potential of PMIF inhibitors.

Researcher(s)

• Promoter: Baeza Garcia Alvaro

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

African trypanosomiasis is a tsetse fly transmitted disease indigenous for the African continent. Millions of people in 36 sub-Saharan African countries are currently at risk of this fatal infection. The current drugs are faced with limitations of toxicity and drug resistance and to date not a single effective vaccine is available. For both vaccine development and elimination endeavours, an adequate understanding of the immunology of infection onset, disease progression and distribution of parasites to tissue sanctuary niches is crucial. Our recent work has identified the skin and lungs as overlooked tissue reservoirs. Although they are sites of strong parasite proliferation, the limited organ-specific pathology has led us to overlook their importance in disease establishment and parasite transmission. Asymptomatic individuals who remain undiagnosed may pose a significant constraint for disease control. Understanding both colonization of skin and lungs as major reservoir tissues and specific parasite adaptations, will support the identification of parasite- or host-specific markers for diagnosis and increase our insight into the immunological basis of increased susceptibility to secondary pulmonary infections. Hence, we will use unbiased approaches linking parasite and tissue transcriptomes and evaluate the use of breathomics as novel diagnostic method.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Lamote Kevin
• Fellow: Mabille Dorien

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis is a major neglected lethal parasitic disease for which treatment options are scarce and toxicity, resistance and post-treatment relapse are common. No human vaccine is currently available and parasite quiescence is completely overlooked in the development of novel vaccination strategies. Our cutting-edge research has recently identified stem cells in the bone marrow as a sanctuary site where parasites can hide and survive drug treatment by transitioning to a quiescent state. Transcriptional profiling of quiescent and non-quiescent parasites provided differential genes, uniquely expressed during quiescence, that constitute attractive therapeutic vaccine antigen candidates. This project will provide unprecedented information about host-pathogen interactions and explore vaccination strategies to prevent relapse by: (i) obtaining essential data on antigenic presentation properties of Leishmania-infected stem cells, (ii) editing parasitic quiescence genes and selecting single domain antibodies (sdAbs) against quiescence gene products, and (iii) exploring immunity to quiescence genes during infection and following immunization. Taken together, it is expected that in-depth understanding of parasitic quiescence and corresponding antigenic/immunogenic properties will be revolutionary for the development of novel therapeutic vaccination strategies that can be incorporated with drug treatment to prevent relapse.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Sterckx Yann
• Fellow: Present Cassandra

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Several RSV vaccine candidates, usually based on a recombinant form of the fusion (F) protein that is locked in the prefusion state, are in advanced stage of clinical development. These vaccines target the elderly and pregnant women despite the fact that the need may be greatest in children. It seems that for RSV, the prefusion F protein does not result in sufficient protective RSV immunity in children and adults, and that a correlate of protection (CoP) in children might be different than in adults. Determining a CoP for children turns out to be very challenging and many inconsistent results have been found. In this project, a comprehensive study will be done to map the antibody repertoire of pregnant women, newborns and young children up to 16 months, a.o. using an extensive panel of RSV F specific monoclonal antibodies. Subsequently, differences in the processing of the RSV F protein in primary epithelial cells of children and adults will be investigated by characterizing the virus in WD-PNECs, focusing on the structure of the F protein and the presence of different epitopes. Antibody repertoires and virus characteristics will be correlated with the onset and severity of RSV infection in children. Finally, monoclonal antibodies will be developed using subtractive immunization to target epitopes that correlate with a protective CoP in children. This will support the ultimate goal to find a CoP in children and will help to accelerate vaccine development in children.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Maertens Kirsten
• Fellow: Schaerlaekens Sofie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis (VL) is among the deadliest neglected tropical diseases worldwide affecting the most impoverished populations. East-African countries accounted for 57% of the VL global burden in 2020. The WHO recently launched a VL elimination plan for East-Africa, with early detection and treatment of VL cases as the backbone to reduce transmission and VL burden. However, due to gaps in diagnostics and inaccessible healthcare the official numbers are just the tip of the iceberg and many patients remain untreated. Molecular diagnostics are promoted but their implementation in resource-constrained setting is very limited. We aim to ameliorate the research capacities and multidisciplinary collaboration of clinical, laboratory and anthropological researchers at Arba Minch University (AMU) and Jinka Hospital in southern Ethiopia to support independent and gender-equal research. Training on molecular techniques, good laboratory and clinical practice, interpretation and communication of results, evidence-based medicine and findings of the study will be organized at AMU and other health facilities. Trainees will train the next generation. In line with the elimination goals, we will define an improved and less-invasive diagnostic algorithm for VL patients which is acceptable and accessible for all. Therefore, a diagnostic study introducing molecular diagnostic in combination with a qualitative study with in-depth interviews of different stakeholders will be conducted. By investing in multistakeholder engagement though a community of practice, including patients, healthcare workers, researchers, policy makers and NGOs, we ensure uptake of research findings into policy and practice. The project is embedded in a DGD-funded sandwich PhD project. The qualitative study will be performed by the Anthropological Department of AMU involving two female master students. Flemish promoters and supervisors are employed by the University of Antwerp and the Institute of Tropical Medicine Antwerp.

Researcher(s)

• Promoter: Berens-Riha Nicole

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Flaviviruses, a large group of arthropod-borne viruses transmitted by Aedes mosquito vectors in both tropical and subtropical areas, pose an increasing threat for human health. Most of the arboviral infections are either asymptomatic or present with rather mild symptoms during the acute phase. Nevertheless, a fraction of the patients develops complications with severe neurotropic illness or hemorrhagic disease in the post-acute phase. As up to 400 million people are infected with a flavivirus annually around the globe, still a considerable number of patients will evolve to more severe disease. Although for dengue virus (DENV) specifically, the vaccine Dengvaxia® was approved for use in several endemic regions, it's administration is restricted to people who experienced a prior dengue infection because of safety precautions. With other flavivirus vaccines in different stages of clinical development and also specific antiviral treatments under development, such as for example the highly potent anti-DENV compound (JNJ-64281802), there is a need for highly specific and sensitive diagnostic tools to enable correct serostatus determination and to triage patients for treatment. Although molecular diagnostic tests based on RT-qPCR have an excellent sensitivity and specificity, their application is limited to the short viremic period and to a laboratory setting that enables molecular testing. To date, the vast majority of the laboratory diagnoses relies on serology based tests, especially in low and middle income countries in endemic areas.(6) Serology is often problematic due to the high antigenic resemblance of co-circulating flaviviruses such as DENV, Zika virus (ZIKV) and yellow fever virus (YFV). In an attempt to overcome these problems, researchers at the Institute of Tropical Medicine (ITM) explored the diagnostic potential of antigenic regions at higher amino acid resolution. Several flavivirus-specific peptides as well as cross-reactive peptides were identified during microarray screenings and confirmed in bead-based multiplex immunoassays, showing a promising improvement compared to the performance of current commercial serological tests for DENV. Starting from the earlier identified peptides for DENV1-4, and based on the expertise and experience of Janssen in biomarker development, we aim to identify peptides for ZIKV and YFV in new microarray screenings, and strive to optimize DENV, ZIKV and YFV peptide biomarkers for diagnostic test development, by detailed epitope identification, by mapping virus-specific and cross-reactive epitopes, and by evaluating single- and multiple epitope-peptide hits in multiplex immunoassays. We aim to convert our findings into applicable immunological test format such as peptide ELISA's and ultimately lateral flow assay (LFAs) that allow to discriminate between DENV serotypes, ZIKV and YFV, as well as employ broadly recognized epitopes (for PanDenv and PanFlavi applications). Finally, we aim to evaluate the prototype diagnostic assay (ELISA or LFA) in a reference setting such as the ITM in Antwerp and in endemic settings in Peru and in the Democratic Republic Congo (DRC).

Researcher(s)

• Promoter: Ariën Kevin

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis (VL) is a lethal parasitic disease facing a rise of treatment failures with current drugs. Major knowledge gaps exist in the basis of treatment failure, representing an essential constraint in the development of long-term effective drugs. Our cutting-edge research has recently identified the bone marrow as a sanctuary site where parasites can hide and survive drug treatment. Combination of large-scale in vivo drug screening and immunophenotyping identified stem cells as highly susceptible host cells. These cells exhibit a unique transcriptional "StemLeish" program and provide an environment for the development of parasite quiescence, a metabolic state that enables survival of drug treatment. This project will provide unprecedented information about the host- and parasite-factors underlying relapse by (i) obtaining essential data on the infection and spreading potential of quiescence-associated traits, (ii) deciphering the role of Stemleish genes in stem cell sanctuary and in stimulation of parasite quiescence, with identification of parasite driver/marker genes, and (iii) exploring the therapeutic and diagnostic applications of these novel targets and biomarkers. Taken together, it is expected that in-depth understanding of the molecular basis of stem cells as a parasite niche will be revolutionary for VL treatment and will generate potential diagnostic/prognostic tools that incorporate host sanctuary properties and parasite quiescence features.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Dirkx Laura
• Fellow: Nicolaes Yasmine

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Nosocomial infections are a major hurdle on intensive care units all over the world. Approximately 10% of the patients who stay two or more days in this unit, suffer from such infections, from which ventilator-associated pneumonia (VAP) is the most common. One of the most threatening bacteria that can cause this biofilm-related infection on the endotracheal tubes is Pseudomonas aeruginosa. The diagnosis is difficult and empirical antibiotic treatment is currently the only initial option during the first acute stage of the disease. This project aims to develop an anti-infective medical device that can be used in a preventive context.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Wouters Milan

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Our understanding of the neutralizing antibody response to the Fusion (F) protein of Respiratory Syncytial Virus (RSV) is still incomplete. The RSV F protein is unique as it contains adjacent to the fusion peptide not one but two furin protease cleavage sites, separated by a 27 amino acid (aa) peptide (p27). Maturation of the protein is associated with removal of p27 from the F protein which also activates the prefusion state. The exact role of p27 and the benefit for the virus are not known. Surprisingly, p27 contains 2 to 3 N-linked glycosylation sites and data from the lab of the promotor show that removal of these glycosylation sites increases neutralizing antibody responses. How removal of glycosylation sites, in a peptide that is considered not to be present in the mature F protein, affects neutralizing antibody responses is unknown. Preliminary data suggest that removal of these N-linked glycosylation sites affects cleavage of the p27 peptide and that this may stabilize the F protein in a flexible prefusion configuration, which may expose novel neutralizing epitopes and increase exposure of known epitopes to the immune system. This hypothesis will be investigated with a combination of in vitro and in vivo experiments using a panel of mutant F proteins, monoclonal antibodies and recombinant viruses. Further, the structure of the flexible prefusion conformation and neutralizing epitopes involved will be identified, which can drive development of novel vaccines.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Jacobs Lotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The collaboration with DNDi is aimed at providing a solid proof-of-concept in in vitro and animal models for the treatment of leishmaniasis with current (pre-)clinical leads and/or with a combination of leads and current reference antileishmanial drugs. Services to support DNDi discovery and development projects will cover in vitro monotherapy profiling against a panel of (resistant) strains, in vivo evaluation in mouse and/or hamster efficacy models including both monotherapy and combination therapy with PK analysis, evaluation of antiparasitic killing kinetics, and evaluation in immunocompromised animal models.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Even after decades of attempted control, tuberculosis (TB) remains the world's deadliest infectious disease. The resistance of Mycobacterium tuberculosis (MTB) to the most powerful anti-TB drug, rifampicin, poses a primary threat to global TB care, with around 500,000 new patients developing rifampicin-resistant TB (RR-TB) worldwide each year. New approaches are needed to close the detection gap of RR-TB and improve treatment success while preventing acquired resistance to 2nd-line drugs. This project will tackle the main current challenges in the field of RR-TB, from diagnosis of patients until confirmed cure. First, I will study the performance of the Xpert Ultra and its impact on the diagnostic flowchart in Rwanda. Secondly, I will be the first to develop and implement an innovative and accessible direct-on sputum phenotypic drug-susceptibility testing (pDST) assay for the detection of resistance to 2nd-line drugs. Once direct pDST is established, I will evaluate its potential to monitor MTB viability and emerging resistance to fluroquinolones and bedaquiline. Finally, I will evaluate the early bactericidal activity of the 2020-WHO-recommended all-oral treatment regimen versus the previous injectable-based regimen. These findings will inform optimal and simplified rifampicin and 2nd-line drug DST algorithm with the aim to achieve the global target 'universal DST' in Rwanda and elsewhere and help identify critical next steps towards safe and effective RR-TB treatment.

Researcher(s)

• Promoter: Rigouts Leen
• Fellow: Cuella Martin Isabel

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Background: Neglected tropical diseases (NTDs) encompass a wide range of communicable diseases that are common in tropical and subtropical regions and affect more than 1 billion people worldwide. NTDs typically have a major impact on low-income countries and pose a major health threat in both developed and developing countries. A typical feature is high morbidity, which has a serious impact on quality of life, social integration, mental health and economic productivity and status. The situation is further complicated by globalization, human migration, climate change and the altered distribution of NTD-transmitting vectors (blood feeding arthropods such as mosquitoes, flies and ticks). As a result, even currently unaffected areas (including Europe) are facing the (re)emergence of NTDs and are at increased risk of becoming endemic. The World Health Organization (WHO) and the goals set out in the Millennium Declaration underline that monitoring NTDs not only has a direct medical impact but is also a strategy for combating poverty. That is why the WHO has listed 20 priority NTDs in the interest of global health and well-being. Two of these, leishmaniasis and human African trypanosomiasis (HAT, sleeping sickness) are at the heart of the research in my research group. Objectives: The parasitology research team I lead at LMPH (LMPH-PAR) uses a two-pronged approach to address NTDs, with an emphasis on drug discovery with novel mechanisms of action and immunoparasitology research. The main aim is to deliver key innovative elements with high translational potential to the next generation of therapies, diagnostics and vaccines using complementary and multidisciplinary approaches. In addition, there are still large knowledge gaps in the highly efficient transmission of parasites by their respective insect vectors, tsetse flies and sand flies. The primary objectives are (i) to understand the immunoparasitological basis of early infection after insect bite, (ii) identification of advanced anti-parasitic lead compounds, (iii) to determine the mechanisms of action of the most advanced leads with an emphasis on deconvolution of the targets, (iv) understanding the basis of treatment failure and the spread of resistance and (v) strategic exploration of innovative vaccines and diagnostic modalities to identify novel vaccine targets and obtain reliable cure tests.

Researcher(s)

• Promoter: Caljon Guy
• Fellow: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project website

Project type(s)

• Research Project

Abstract

The FWO Scientific Research Network brings together Flemish experts and their international connections in a consortium that is able to study different crucial aspects of viral diseases of man and animal and to identify novel targets for the generation of vaccines and antiviral drugs. The consortium consists of members who are active in virus characterization, virus-host interactions and pathogenesis, virus evolution and spread and development of vaccines and antivirals.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project website

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The aim of this research community is to better understand the formation and the structure of bacterial and fungal biofilms in humans. This could lead to a more efficient treatment of biofilm-related infections.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Despite recent progress in biomedical research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is still the world's leading infectious disease killer worldwide. Treatment options are limited, and expensive, recommended medicines are not always available in many countries, and patients experience many adverse effects from the drugs. Thus, there is an acute need for the development of a novel combination regimen with an indication for effective, shorter, and safer treatment of all forms of TB. The overall objective of RESPIRI-TB is to find new drug candidates as potential components of a new, more efficient combination drug regimen against TB that is less prone to resistance and allows shortening of treatment duration for TB, and multidrug-resistant TB. Such a drug combination will synergistically target the energy metabolism of Mtb or complementary targets. To achieve this, we will advance recently discovered inhibitors of the Mtb respiratory pathway. In addition, we will target the Mtb specific molecular mechanism that reduces reactive oxygen species in the cell.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

West Nile virus (WNV) and Usutu virus (USUV) are two mosquito-borne flaviviruses that are emerging in Europe, posing an increasing health risk. Given the increasingly imminent danger that these viruses represent, it is necessary to find both more efficient methods for early diagnosis and therapeutic or preventive solutions to curb the impact of these pathogens on human health. Non-structural protein 1 (NS1) of WNV and USUV is considered a promising target for diagnostic, vaccine, and therapeutic development. The project aims to produce monoclonal antibodies (mAbs) that are highly specific for NS1 of WNV and USUV using a subtractive immunization approach and to set up an expression system for recombinant flavivirus proteins that preserve the original oligomerization state of NS1, which circulates in the blood as a hexamer. The generated mAbs will drive the development of the next generation of diagnostics, and this will give us a competitive edge toward follow-up project applications and negotiations with diagnostic assay developers. Furthermore, the antibodies and recombinant proteins can contribute to elucidating the role of NS1 in vaccine and therapeutics development, constituting the necessary preliminary data to proceed with broader project proposals.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Arthropod-borne flaviviruses represent an increasingly urgent threat even in Europe, where West Nile virus (WNV), Tick-borne encephalitis virus (TBEV), and Usutu virus (USUV) already co-circulate. Furthermore, human travel from endemic areas periodically introduces other flaviviruses, like the Japanese Encephalitis virus (JEV). Distinguishing between these neurotropic flaviviruses is becoming crucial because an early and precise diagnosis of flavivirus infection can improve infection prevention and clinical management. The presence of the viral non-structural protein 1 (NS1) in the blood can be determined even before symptoms appear, which makes it a promising biomarker for developing an antigen capture-based assay. The lack of specific monoclonal antibodies against NS1 on the market is the main reason why NS1 diagnostic tests are not commercially available for JEV, WNV, TBEV, and USUV. I will produce and characterize a panel of monoclonal antibodies (mAbs) specific for the NS1 protein of these viruses using a subtractive immunization strategy. The mAbs will be tested and validated for the development of diagnostic tests that allow the discriminating of the flavivirus responsible for the infection unequivocally. The development of novel diagnostic techniques that can significantly enhance the detection of flavivirus infection will be made possible by the manufacture of this unique pool of mAbs.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Ceconi Martina

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In the frame of a fee-for-service agreement, UAntwerpen shall perform certain services namely 'Evaluation of the antileishmanial potency of an active pharmaceutical ingredient in a hamster model of visceral leishmaniasis'.

Researcher(s)

• Promoter: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Human African trypanosomiasis is a tsetse fly-transmitted disease indigenous for the African continent. Millions of people in 36 countries in sub-Saharan Africa are currently at risk of this often fatal infection. The drugs that are currently available are faced with limitations of toxicity and drug resistance and not a single effective vaccine is yet available. For both vaccine development and elimination endeavours, an adequate understanding of the immunology of infection onset is crucial. Mast cells (MCs) are immune sentinels in the skin that are amongst the first to contact the Trypanosoma parasite following a tsetse fly bite. These cells play major roles in orchestrating early inflammatory responses, regulating vascular permeability and influencing immunity development in lymph nodes. Despite seminal work in mosquito-transmitted viral diseases, MCs remain underexplored as target cell during parasitic infections. Combining our expertise in MCs and our work with Trypanosoma as well as the possibility to use the natural vector in our inhouse insectary, the role of MCs will be assessed in natural Trypanosoma infections. Using human MCs derived from progenitors in donor blood, a battery of cellular activation markers will provide insights in the interaction with the Trypanosoma parasite and tsetse fly-derived components. The mast cell role will be further explored in appropriate animal models of mast cell deficiency following a natural infection by a tsetse fly bite. To summarize, the preliminary results of our in vitro and in vivo experiments will provide insight towards novel intervention strategies and foundations for future research.

Researcher(s)

• Promoter: Mabille Dorien

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

With this project, we will establish a Respiratory Virus Repository at the University of Antwerp. The collection of respiratory viruses will be available to companies, academic groups, and research institutions.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: De Winter Benedicte
• Co-promoter: Van Hoorenbeeck Kim
• Co-promoter: Verhulst Stijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The research aims at improving an existing EU project application on the development of in vitro and in vivo models to quantify nucleic acids internationalization in live bacterial cells, and thereby preparing it for resubmission in a next round. This research will have a major contribution to the discovery of novel antibacterials. The budget will be used primarily for the compilation and interpretation of preliminary data from new experiments, with a focus on the development of bioluminescent bacterial strains for in vivo research.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Human respiratory infections lead to a spectrum of respiratory symptoms and variable disease severity, contributing to substantial morbidity, mortality and economic losses worldwide. Respiratory pathogens can spread easily in the population and are specifically prone to cause large scale outbreaks, epidemics and even pandemics. While such pandemics have devastating impact on human health and cause major socio-economic disruptions, the annual burden of respiratory infections such as Respiratory Syncytial Virus (RSV), Mycobacterium tuberculosis and Streptococcus pneumoniae is also substantial. Respiratory infections are worldwide the number one cause of death in children below five years of age, with ~650.000 annual deaths. The disease burden however goes beyond this staggering number, with an overall effect on morbidity and mortality in the general population worldwide (~2.5 million deaths annually). Of particular interest, it has become very clear that severe disease upon respiratory infections not only depends on one particular pathogen, but also depends on other previous or simultaneous co-infections. The importance and impact of co-infection are however not yet fully clear. Therefore, there is an urgent need to enhance our understanding of host-pathogen interactions at the lung (immune) interface and to develop clinically relevant animal models. Laboratory animal studies are a cornerstone of basic research and the development of novel prophylactic, diagnostic and therapeutic modalities. However, the development of suitable infection models can be notoriously daunting, often resulting in very narrow assay windows due to rapid pathogen clearance or early mortality of the host. The research teams involved in this challenge have longstanding expertise with infection models, both in vitro and in rodents. Three PIs focus their research on parasitic (prof. Caljon), viral (Prof. Delputte) and bacterial infections (Prof. Cos) to gain understanding of protective innate and adaptive immune responses, and of (immune) pathology. A recent study in which LMPH was involved demonstrated that some lung bacteria have an immune modulatory role in chronic respiratory diseases (Rigauts et al., Eur. Resp. J., 2022). Very recent parasitological observations show that African trypanosomes rapidly and permanently colonize the lung tissue with substantial changes in the immunological repertoire (reductions in B cells and eosinophils) but without overt respiratory dysfunction or pathology. Surprisingly, RSV challenge revealed a higher susceptibility with an enhanced and sustained viral replication, hinting at complex in vivo interactions that cannot be modelled in vitro (Mabille et al., Nat. Commun., pending acceptance). Exploiting the expertise with parasitic, viral and bacterial infections at LMPH, the established high-end platforms for evaluating lung function and immunological correlates and initiatives of biobanking, this challenge aims to functionally and immunologically characterize pulmonary infections and co-infections of parasitic, viral and bacterial origin. This will provide invaluable information on virulence and pathogenicity of selected strains from in-house collections, establishment of in vivo read-out assays and immunological correlates of induced pathology. Besides progressing basic scientific insights in host-pathogen interactions, the applications are numerous including the development and evaluation of diagnostics and medicinal compounds.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter
• Fellow: Araujo Sergio

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This application relates to the purchase of new basic research infrastucture, a device for versatile Single Cell Sorting and Dispensing using Microfluidics. The equipment can be used for a variety of applications, including cell line development, monoclonal antibody development, iPSC cloning, single cell omics, rare cell isolation, microbiology, virology, immunology and microbial technology. The equipment works at low pressure and allows easy setup and easy switching between a variety of applications, both with or without infectious agents.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Cos Paul
• Co-promoter: Lebeer Sarah
• Co-promoter: Ogunjimi Benson
• Co-promoter: Vorsters Alex

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The current application envisages extending the infectious disease and inflammation research and drug discovery platforms at the University of Antwerp to accommodate highly flexible and versatile live cell imaging and biochemical read-outs with a possibility to upgrade from median to high throughput. The apparatus will be embedded in a high-end immunoprofiling platform and BSL-2 environment at the Laboratory of Microbiology, Parasitology and Hygiene (LMPH) with biosafety approvals for basic research on infection with microbial pathogens. The TECAN SPARK Cyto 600 is a highly versatile multimodal plate reader that enables cellular and in situ molecular assays in controlled O2/CO2, humidity cassette and temperature regulation environments with real-time absorbance, fluorescence and luminescence measurements. Three different optical measurement options exist by using filters, monochromators or fusion optics which eliminates the compromise between sensitivity and flexibility. The unique lid-lifting function enables substrate addition or immune cell priming through the included 2-channel injector. SPARK Cyto 600 is equipped with 2×, 4× and 10× objective lenses and a CMOS camera to enable live cell imaging. In addition to bright field imaging, fluorescence imaging is possible in 4 optical channels with capability of Time-Resolved Fluorescence (TRF) and Fluorescence Resonance Energy Transfer (FRET). An additional asset is the compatibility with bead-based proximity assays using Alpha Technology with optimized integrated filters and laser-based excitation. While all known competitors limit live cell imaging systems to bright field and fluorescence measurements, the SPARK Cyto 600 also allows for real-time detection of glow and flash luminescence signals and Bioluminescence Resonance Energy Transfer (BRET) applications to enable sensitive real-time follow-up of protein-protein interactions in cells. Given the high versatility and pressing need for such equipment for infection and inflammatory disease research, this unique apparatus will allow real-time imaging of cellular as well as molecular events in controlled conditions. This new infrastructure will therefore boost research of many research groups at the University of Antwerp and will contribute to fundamental insights at the cellular and molecular level as well as to the development of novel therapeutics and diagnostics.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Augustyns Koen
• Co-promoter: Sterckx Yann
• Co-promoter: Vanden Berghe Wim
• Co-promoter: Wullaert Andy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Since the beginning of the COVID-19 pandemic, the wastewater-based epidemiology (WBE) of SARS-CoV-2 has been used as a complementary indicator to follow up on the trends in the COVID-19 spread in Belgium and in many other countries. To further develop the use of WBE, a multiplex digital polymerase chain reaction (dPCR) assay was optimized, validated and applied for the measurement of emerging SARS-CoV-2 variants of concern (VOC) in influent wastewater (IWW) samples.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Neurotropic viral infections continue to cause major disease and economic burden. Such infections are most commonly caused by herpesviruses, arboviruses and enteroviruses, often leading to severe neurological damage with poor clinical outcomes. The search for interventions to prevent and/or treat these infections is however challenging. The main reason for this is the nature of the target cells, neurons, which are chiefly non-renewable and drastically differ from other cells (or cell lines). Discovery of novel antivirals via the classically performed research with cell lines, is not appropriate for viruses that infect neurons. Highly specialized, bona fide, human neuronal culture models are imperative. With this project, we will develop specialized neuronal cultures aimed at higher throughput antiviral screening.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Ogunjimi Benson
• Co-promoter: Ponsaerts Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The predominant Leishmania transmission route is through a bite of female sand flies. However, studies conducted on dogs and case reports from humans suggest that immunocompromised visceral leishmaniasis (VL) patients might also be able to transmit Leishmania parasites through sexual intercourse. We aim to initiate an unprecedented pilot study to gather preliminary evidence on parasite presence and persistence in the semen of male VL-HIV patients and its underlying pathophysiology. First, we will perform a qualitative study to gather perspectives of health care workers and patients regarding semen sample collection to develop appropriate operating procedures in suitable conditions. Second, 15 VL-HIV patients will be recruited, clinically examined and viable Leishmania parasites will be measured in semen samples prior to and post treatment. The immunological and histopathological impact of semen parasite infiltration will be assessed in detail in an immune-competent and -compromised hamster model and by measuring corresponding inflammatory and oxidative stress markers in patients' semen. If parasite infiltration and persistence can be shown, this proof-of-concept study in humans and rodent models would significantly increase our competitiveness to apply for a more comprehensive study on the prevalence of sexual transmission and impact on fertility.

Researcher(s)

• Promoter: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This research project focuses on dry eye disease (DED) which is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. DED can be divided into tear-deficient and evaporative types. Evaporative dry eye can be divided into Meibomian gland disease (MGD) and exposure-related dry eye. MGD is the most common cause of evaporative DED and it is defined as "a chronic, diffuse abnormality of the Meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion". Research on the MGD is a priority. An appropriate animal model is an essential tool for translational research with the final goal to find better treatments for DED. This project is a continuation of the MSCA-ITN IT-DED3 project. One of the biggest challenges is to evaluate the cytokine profile in a low amount of rat tear fluids. Preliminary results with a customized multiplex (3plex) Enzyme Linked Immunosorbent Assay (ELISA) are promising and the assay will be further optimized and validated. The evaporative dry eye animal model will be further optimized based on the previous results. To minimize the number of animal experiments, a cell culture model in which DED is induced through the use of hyperosmolar stress is also under development and focuses on monocytes and corneal and conjunctival epithelial cells. This will allow us to test the most promising anti-inflammatory compounds for their antioxidant activity in a cellular model.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Compagnone Agnese

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Tracking the presence of SARS-CoV-2 in wastewater allows to monitor the spread of the virus in the population at regional and subregional level, several days earlier compared to data obtained from screening of patient samples. This wastewater monitoring is no replacement for current clinical testing, yet it is pivotal in early detection of future changes in the epidemic and the tracking of novel outbreaks in specific regions. With this project we will detect SARS-CoV-2 in sanitary wastewater from larger complexes, this to evaluate the feasibility and value of increasing the granularity of monitoring points for surveillance.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Despite a global distribution of Leishmaniasis and 1.5 to 2 million new cases annually, no effective human vaccines are available and treatment failure with current drugs is on the rise. Mast cells (MCs) are immune sentinels in the skin that are amongst the first to contact the Leishmania parasite following a sand fly bite. These cells play major roles in orchestrating early inflammatory responses, regulating vascular permeability and influencing immunity development in lymph nodes. Despite seminal work in mosquito-transmitted viral diseases, MCs remain underexplored as target cell during parasitic infections. Combining the strengths in immunology, parasitology, transcriptomics and biostatistics, the role of MCs will be assessed in natural Leishmania infection. Combining digital transcriptomic data from large human cohorts and experimental mouse infections, will enable detailed cross-species and multi-tissue insights into MC responses across the whole clinical spectrum of leishmaniasis. Using human MCs derived from progenitors in donor blood, a battery of cellular activation markers and specific silencing of MC gene expression using an in-house, cutting-edge method will enable unprecedented mechanistic insights in the interaction with infectious agents, i.e. Leishmania spp. parasites. This may provide new biomarkers for clinical follow-up as well as novel therapeutic targets that will be explored in the appropriate animal models of leishmaniasis initiated by a sand fly bite.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Ebo Didier

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Tracking the presence of SARS-CoV-2 in wastewater allows to monitor the spread of the virus in the population at regional and subregional level, several days earlier compared to data obtained from screening of patient samples. This wastewater monitoring is no replacement for current clinical testing, yet it is pivotal in early detection of future changes in the epidemic and the tracking of novel outbreaks in specific regions. As such this testing will contribute to a proactive management and containment of the epidemic.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: van Nuijs Alexander

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Plasmodium falciparum parasites (causing more than 500,000 deaths each year) are transmitted from human to human via gametocytes (i.e. the sexual and only transmissible parasite stages) which are taken up by mosquitoes during a blood meal. A small fraction of parasites convert to gametocytes at every life cycle; nevertheless our understanding of which factors influence this decision and increase parasite conversion to gametocytes is poorly understood. In this project, we aim to investigate whether host and parasite genetics alter gametocyte conversion and if host anti-gametocyte immunity modifies gametocyte carriage (i.e. the gametocytes burden in peripheral blood) . We will use recently developed in vitro conversion assays and establish a novel ex vivo conversion assay, to measure the effect of host and parasite genetics on gametocyte conversion within P. falciparum transgenic lines as well as in field isolates. Furthermore, the potential contribution of host immune responses to the carriage of circulating stage V gametocytes will be assessed with immunological assays. We expect that the outcomes of this project will guide the development of new targets and tools (e.g. drugs and vaccines against the transmissible stages of the parasite) and will provide the knowledge to improve malaria transmission-blocking interventions.

Researcher(s)

• Promoter: Caljon Guy
• Fellow: Drissi El Boukili Yasmina

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Streptococcus pneumoniae is an important human pathogen, as it is one of the most common causes of community-acquired pneumonia and otitis media. Several issues arise when battling these infections. First, replacement of vaccine-serotypes by new ones has been observed. Second, antibiotic resistance is an emerging problem. Also, antibiotic persistence is considered an important, yet underexposed phenomenon. Persister cells are a subpopulation of cells that are tolerant to lethal concentrations of antibiotics and are involved in a variety of chronic and recurrent infections. However, little to nothing is known about persister formation in S. pneumoniae. This project aims to fill this gap in knowledge. As in vitro autolysis hampers the prolonged monitoring of cultures, a variety of strategies – including the generation of mutant strains – will be applied to overcome this issue. Using heritability assays and gene sequencing to exclude arising of antimicrobial resistance, the presence of persisters will be confirmed. Furthermore, an in vivo model for persister studies will be optimized to confirm the clinical relevance of in vitro results. Lastly, the propensity to form persisters, the antimicrobial susceptibility profile, the strain origin and the in vivo virulence of a set of 50 clinical isolates will be evaluated. Collectively, this project will significantly progress our understanding of importance of persisters in the pathology of S. pneumoniae infections.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Geerts Nele

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Biofilm formation during lung infection is related to persistent infection. This is a characteristic of chronic diseases such as Cystic Fibrosis (CF). Moreover, biofilm formation in endotracheal tubes (ETT) is related to the onset of Ventilator-Associated Pneumonia (VAP). Failure in treatment is associated with high morbidity and mortality. In addition to increased resistance, antibiotic therapy failure can also result from regrowth of a subset of cells in bacterial populations that are called persisters. When challenged with a lethal dose of antibiotics, this small fraction of transiently antibiotic tolerant cells survives to give origin to a new population and they are then related to the chronic nature of pneumonia. Therefore, new ideas to prevent and treat biofilm-related lung infections are required. New antibacterial targets and incorporation of antibacterial compounds in 3D printed catheters are being investigated. A chronic P. aeruginosa lung infection model, based on intratracheal infection of bacteria encapsulated in seaweed alginate beads, was optimized to characterize persistence in collaboration with KULeuven. This animal model mimics cystic fibrosis (CF) and several low and high persister laboratory strains are currently being studied in vivo to validate the infection dose and the treatment scheme for persistence studies. Natural isolates from other clinical settings, including animal and environmental origin, will also be tested. The VAP model is in the framework of an H2020 ETN project called PRINT-AID. The aim of this project is to proof the value of developing a new generation of 3D-printed personalized medical devices with antimicrobial functionalities. Screening of new drug leads, in vitro testing in dynamic biofilm systems and cell models and improvement of the manufacturing process of 3D printed and coated catheters are currently being performed by collaborators. UAntwerp will be responsible for the development of a VAP mouse model in which the 3D produced tubes will be inserted in the main bronchus intratracheally. The tubes will be inoculated with biofilm-forming S. aureus and with this model we aim to evaluate the inhibition of bacterial adherence to the tubes in vivo and the anti-infective efficacy of the tubes by assessing the bacterial burden in the lungs.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Tracking the presence of SARS-CoV-2 in wastewater allows to monitor the spread of the virus in the population at regional and subregional level, several days earlier compared to data obtained from screening of patient samples. This wastewater monitoring is no replacement for current clinical testing, yet it is pivotal in early detection of future changes in the epidemic and the tracking of novel outbreaks in specific regions. As such this testing will contribute to a proactive management and containment of the epidemic.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: van Nuijs Alexander

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The main goal of SPRINGBOARD project is to strengthen research potential of the Latvian Institute of Organic Synthesis (LIOS) through establishing long-lasting and sustainable collaboration network with the leading European research institutions – University of Antwerp, University of Copenhagen, University of Florence and University of Helsinki – in the area of advanced discovery and design of novel antibacterial drugs.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Recently, we have obtained a Respiratory Syncytial Virus (RSV) isolate with unique characteristics for applications in pre-clinical and clinical research. With this project we aim to gather additional knowledge on this primary isolate and to identify genomic changes responsible for the observed phenotype.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Additive manufacturing (AM) technologies have been extensively used in many fields and applications. Personalized medicine is one of the most promising fields that could benefit from such technologies. The Food and drug administration (FDA) approved in 2016 the first drug loaded device produced via AM introduced by Aprecia Pharmaceuticals. Fused filament fabrication (FFF) is one of the AM technologies that rely on the extrusion of a melted polymeric material through a nozzle. The consecutive movement in three-dimensional space while extruding material results in producing objects with high geometrical complexity. Such produced objects were not possible to build through conventional manufacturing technologies. This technology specifically has high potential in the pharmaceutical sector as it relies on a well-known technology used for producing drug loaded polymeric formulations, called hot melt extrusion (HME). In this technology a carrier polymer is mixed with a known active pharmaceutical ingredient (API) using a screw extrusion system and then hot extruded through a die for further processing. This project is a continuation of the PrintAID ITN-project. It aims at utilizing 3D-printing technologies for printing anti-infective medical devices. These devices should have the ability to prevent biofilm-related infections. Selected antibacterial agents will be analyzed for their thermal stability as the 3D printing process uses heat for processing. On the other hand, thermoplastic polymers will be investigated for their mechanical, rheological and thermal properties and the best ones will be selected as carrier for the antibacterial agents. The fused filament fabrication 3D printing technology will be modified and used to produce medical devices using the selected formulation. The modification will focus on reconfiguring the extrusion system to convert it from a conventional filament extruder to a pellet extruder, thereby providing more versatility in material selection. These devices will be analyzed in terms of mechanical integrity and formulation stability. in vitro and in vivo samples will be produced to study the release profile and the killing efficacy of the selected APIs. The intended goal is to produce proof-of-concept devices to tackle bacterial-associated infections on indwelling devices such as endotracheal tubes.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Within ongoing collaborative research with the Lab. of Medicinal Chemistry (UGent), a series of novel nucleoside analogues was identified to have potent and selective in vitro activity against African Trypanosomes, which was also confirmed in vivo in an acute and a chronic mouse model of Trypanosoma brucei. A basic dataset supporting early preclinical exploration is already available: oral availability, metabolic stability, blood-brain barrier passage, cidal and curative potential and mechanism of action. Project valorization potential must currently be situated in the veterinary application area in view of its economical and societal impact, and much less in the human application. In order to formally upgrade this project to 'drug development candidate' status, additional preclinical exploration is required to reach a go / no-go decision and trigger a commitment of a committed public-private partnership (GALVmed). In line with their preferred target product profile (TPP), the proposed research will involve in vitro and in vivo pharmacology extended to the animal trypanosome species, absorption and elimination pharmacokinetics after oral and parenteral (single dose) administration, in vitro metabolic half-life in the target animal species (cattle, horse), genotoxicity (Ames test) and short term (2w) repeated-dose toxicity in mice.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project entitled "The Exploration of novel rapid technologies and alternatives to conventional microbiological test approaches" will explore new methodologies to replace conventional microbial quality testing methodologies.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Leishmaniasis is a neglected tropical disease which is transmitted through the bite of female sand flies of the genera Phlebotomus and Lutzomyia. Leishmania infection might provoke several changes in the fly's feeding behaviour, such as an increased biting persistence and a greater tendency to feed on multiple hosts, hereby enhancing parasite transmission. However, recent evidence from malaria research now indicates that the composition of the blood meal might have an equally important impact on vector behavior and parasite transmission. Although the involvement of the host's glucose/insulin metabolism is well-accepted for malaria, its potential involvement in Leishmania infection in vivo has barely been investigated before. This project will aim to evaluate the effects of the overall infection burden in the host on (1) the glucose/insulin levels in host blood; (2) the host's attractiveness and transmission potential to naive sand flies; and (3) sand fly survival, sand fly infection dynamics and final transmission potential with emphasis on the role of glucose/insulin.

Researcher(s)

• Promoter: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This application relates to the purchase of new basic infrastructure, more specific a FlexiVent system from Emka Technologies. FlexiVent is a platform for standard respiratory research that can be used across many pulmonary applications and which has major advantages compared to the classical, non-invasive, unrestrained plethysmography because it is accurate, reproducible and proven. FlexiVent is much more capable of detecting pulmonary abnormalities via changes in functional residual capacity, total lung capacity, vital capacity, and compliance of the respiratory system. Furthermore, analysis of pulmonary functions via FlexiVent allows distinction between respiratory diseases in mice by clinically relevant variables and is therefore generally accepted as the standard in the functional evaluation of infectious and non-infectious pathological, respiratory disease models.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Delputte Peter
• Co-promoter: Verhulst Stijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Pulmonary infections caused by the Mycobacterium avium–intracellulare complex (MAC) are slow and progressive, and increasingly prevalent in developed countries. They can be cured, but their treatment consists of a 12 months multidrug regimen. A key issue standing in the way of designing more effective treatment regimens is the lack of a diagnostic tool for drug susceptibility testing (DST) in MAC. Current methods are slow (3-5 weeks), poorly reproducible and their results are difficult to interpret by clinicians. In this project, we will design a novel DST for MAC infections. It is based on the idea that a susceptible bug will feel stress under attack of an antibiotic, and a resistant one will not. The test is based on multiplex measurements of relative quantities of antibiotic-specific RNA biomarkers after short exposure to the drug. This test is unlike any test on the market. The project start fundamental, with transcriptional analyses of MAC cells under antibiotic stress. We will identify drug-specific sets of stress genes, and convert these into a Luminex-based format for multiplex quantification. The test parameters will be optimized using contemporary clinical strains, in collaboration with the National Reference Centre for Mycobacteria. Finally, we will apply our platform to identify synergetic interaction between novel and old compounds to derive optimal drug combinations with the strongest possible effect on clinical MAC strains.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Sury Amandine

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

There is growing conviction that certain parasites successfully initiate infection in the skin by specifically targeting and co-opting immune cells present or recruited to the dermis following inoculation by their arthropod vector. One such pathogen is the protozoan parasite Trypanosoma brucei which causes sleeping sickness and is inoculated by the tsetse fly. These inoculated parasites are peculiarly infective despite the rapid recruitment of activated innate immune cells at the inoculation site, revealing that the parasite has evolved powerful mechanisms to either evade or overcome the host's vigorous innate immune response. Extracellular vesicles (EV) are believed to play a major role in this parasite-host interplay. Novel cutting-edge technologies are required to gain fundamental insights in the role of parasitic EV proteins because current gene editing and silencing methodologies happen to be inappropriate. Using Nanobodies, this project will develop a strategy to selectively deplete proteins from the EV cargo to allow detailed scrutiny of the molecular players involved in the parasite-immune cell interaction. The impact of EV proteins on kinase activity fingerprints of innate immune cells and their role in a vector-based parasite transmission cycle will be assessed. Collectively, this project will significantly progress our understanding of fundamental aspects of the trypanosome-host interaction.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Sterckx Yann
• Fellow: Claes Mathieu

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Worldwide, pulmonary disease caused by members of the Mycobacterium avium complex (MAC) is increasing. Treatment of MAC lung disease requires a multidrug chemotherapy that takes up to 12 months and often leads to adverse drug effects, treatment failure, MAC reinfection and the emergence of drug resistance. New strategies need to be explored that can lead to more successful treatment of MAC infection. Mycothiol cysteine ligase (MshC) and the mycothione reductase (Mtr) are two key enzymes of the bacillary redox homeostasis and are unexploited drug targets. We hypothesize that these genes play an essential role for both the virulence and the stress tolerance within MAC and that targeting these genes would synergize with existing and emerging antimycobacterial therapeutics. In this project proposal we aim to investigate these hypotheses by the generation of a panel of recombinant MAC strains in order to study the impact of the target genes on the physiological growth, stress tolerance, cellular and in vivo virulence and synergy with existing and emerging MAC therapeutics. The findings can support future target-based drug development programs of potential Mtr and MshC inhibitors. In the long run, the findings within this research could lead to a safer, shorter and more cost-effective treatment of MAC infection.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Piller Tatiana

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The objective of this project is to elucidate the exact molecular MOA of small-molecule polymerase inhibitors of RSV and hMPV. This research will significantly increase the field's understanding of how these small-molecule replication inhibitors work and ultimately contribute to providing a new and highly effective treatment strategy for RSV and hMPV. More precisely, this projects aims to: (i) elucidate the precise molecular effects of small-molecule polymerase inhibitors of RSV and hMPV, (ii) study the mechanisms by which potential resistance may emerge against these inhibitors and (iii) contribute to the elucidation of the structures of the full-length RSV and hMPV polymerases by discovering conformation-stabilizing antibodies, that can be used in crystallization or cryo-EM approaches; and by measuring the extent of the stabilizing effects of these antibodies and small-molecule inhibitors, enabling optimized design of drug candidates. To do so, we will use, develop and exploit challenging and innovative techniques to find an effective treatment for RSV and hMPV infections.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Bonneux Brecht

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Black Soldier Fly Larvae (BSFL) are larvae from the insect the black soldier fly. They are currently being reared on a global industrial scale as a feed ingredient. They can be reared on a wide range of side and waste streams from food industry and agriculture, being converters of these streams into valuable biomass. Given the struggle of our food system to sustainably meet the protein demands of the growing world population, BSFL rearing offers an innovative, bio-based alternative contributing to a circular economy. As insect production is a novel branch of livestock production, it is up to (academic) researchers to gather the same level of in-depth knowledge that is available for other farm animals on production safety and optimization. For example, the impact of the chemical and microbial composition of the feed on the zootechnical performance and on the microbial safety of BSFL is virtually unknown. Furthermore, preliminary research points towards high value applications for other industrial sectors, such as the pharma and waste treatment sector, that could generate more profit for the insect production sector. This project aims to generate more fundamental knowledge that could support the insect sector, legislation and the co-emerging food value chain to remove legislative and technical hurdles in rearing and valorisation. More specifically, we will explore the hardly investigated interaction between the BSFL, their substrate and their gut microbiota. Such interactions are expected to depend on the substrate and affect (i) the growth of the larvae, (ii) their microbial safety, and (iii) their chemical safety. The overall goal of this project is to define and characterize a set of microorganisms that can be used to manipulate the gut microbiota of BSFL in order to boost its performance in each of the three aforementioned domains and increase their economic value.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In this project, we will confirm the anti-inflammatory effects of Rothia mucilaginosa in complex and physiologically relevant in vitro models of CF and COPD lung inflammation, as well as in in vivo mouse models. The anti-inflammatory compound(s) produced by this bacterium will be identified and the mode of action unveiled.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a major public health hazard throughout the world and was responsible for more than 1.7 million deaths in 2016.The prevalence of drug resistance in Mtb calls for the legitimization of new and highly specific drug targets, focusing on unique pathways.The project encompasses a multidisciplinary approach to disturb the redox homeostasis in Mtb, in an effort to uncover new drug leads for fighting this deadly infection.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Co-promoter: De Winter Hans

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are transmitted by sand flies. Paromomycin (PMM) is used to treat VL patients but was experimentally shown to rapidly induce resistance when applied as a single therapy. We have recently observed that parasites overcome elimination by PMM by hiding in the bone marrow (BM) from where the host can be recolonized. Using combined bioluminescent/fluorescent L. infantum reporter lines with differential susceptibility to PMM, this project will make an in depth analysis of the different cell types in the BM that are infected with L. infantum. Parasite survival in various BM cell types will be evaluated to identify potential sanctuary cells. Parasite isolates from the BM of mice and human patients will be used to explore the acquisition of PMM-resistance in relation to parasite virulence. Infectivity for macrophages and transmissibility by sand flies will serve as indicators for the likelihood of posttreatment parasites to spread. Parallels with treatment of myeloid leukemia, indicate that modulating a specific pathway in hematopoiesis that regulates the BM cellular composition could enhance the efficiency of chemotherapy for VL. Collectively, the proposed multidisciplinary approach will improve our understanding of the complex interactions between the parasite, its host and the drug and will allow the formulation of recommendations for improved treatment interventions.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Dirkx Laura

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Parasites of the L. donovani complex generally cause severe, life-threatening visceral infections in which the spleen, liver and bone marrow are severely affected. In some cases, infections only result in mild transient cutaneous lesions. The exact reasons why certain Leishmania species remain in the dermis and do not migrate to the internal organs are still largely unknown. Although several parasite-related factors have already been suggested, the involvement of the host and vector have been largely ignored. Next to some phenotypic parasite traits, such as infectivity and multiplication potential, this aberrant skin tropism might be linked to the ineffective development of granuloma in the skin, which generally clear the parasite burden in the skin, driving infection into the viscera. In this project, the complex interplay between the parasite's (epi-)phenotype, the drug and the host's immune reaction will be explored using dermotropic VL strains derived from cutaneous or visceral infections. The impact of the development of skin granulomas upon infection with the different strains will be compared in relation to their tissue tropism and in vivo drug efficacy and relapse potential.

Researcher(s)

• Promoter: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Leprosy is a serious mutilating disease and although Mycobacterium leprae was the first human pathogen discovered, the precise way of spreading between humans remains a mystery. This is part of the reason why leprosy control fails despite the availability of effective treatments. Over 200,000 new leprosy patients are diagnosed worldwide each year, and the high proportion in children indicates its ongoing spread. To stop transmission chains once and for all, new approaches to leprosy control are needed. Therefore, this study will revisit fundamental questions regarding transmission in an innovative way. Firstly, we will evaluate minimally invasive, field-friendly tests to quantify the bacillary load in each patient and correlate with the effectiveness of treatment and the identification of the most infectious patients. In this study, we will be the first to apply targeted Next Generation Sequencing of M. leprae. Within the ongoing "ComLep" study in the Comoros, we will classify the bacteria in M. leprae subtypes and associate them with the GPS data of each patient's house, to identify transmission links. Once these transmission chains have been established, we can determine define where transmission occurs and if a reservoir of asymptomatic people is sustaining transmission of the disease. This in turn will inform which contacts should receive leprosy preventive therapy. These findings will inform optimal control strategies to eliminate leprosy in the Comoros and elsewhere.

Researcher(s)

• Promoter: Rigouts Leen
• Fellow: Braet Sofie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are able to survive inside macrophages. Miltefosine is an oral drug used to treat VL patients but is increasingly failing to permanently clear parasites from the patient. Parasites from these relapse patients do not seem to display an increased resistance to the drug but are able to modify the immune system to promote survival inside macrophages even in conditions where the drug is administered. The impact of drug treatment on parasite survival will be evaluated in various tissues using molecular and imaging technologies in rodent models of VL following a natural parasite transmission. Combination of this information with the quantification of drug levels in these tissues, will allow to pinpoint in which tissues parasites are most likely to survive drug treatment. The expression of genes following infection and drug treatment will be analyzed inside infected liver macrophages (Kupffer cells, KCs) in order to understand how parasites from relapsed patients can survive inside host cells. Using transgenic mouse models, this research will allow to evaluate the impact of KCs and KC gene expression on infection and treatment outcome. Collectively, the proposed multidisciplinary approach will improve our understanding of the complex interactions between the parasite, its host and the drug and will allow the formulation of recommendations for improved treatment interventions.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Van Bockstal Lieselotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The EMJMD entitled "Leading International Vaccinology Education" and called "LIVE" is a two-year multidisciplinary Master of Science in Biomedical Sciences delivering 120 European Credit Transfer System (ECTS) under the joint supervision of five Higher Education Institutions (HEIs) from three Programme Countries (ProgC): Universitat Autònoma de Barcelona (UAB) & Universitat de Barcelona (UB) from Spain, University of Antwerp (UAntwerp) from Belgium, and Université Jean Monnet Saint-Etienne 1 (UJM) & Université Claude Bernard Lyon 1 (UCBL) from France.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Education Project

Abstract

This project represents a formal research agreement between UAntwerpen and on the other hand the client. UAntwerpen provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Leishmania donovani is a protozoan parasite that is usually the causative agent of visceral leishmaniasis (VL), an infectious disease which is fatal if left untreated and affects internal organs such as liver, spleen and bone marrow. In some cases, however, infection with this specific parasite species is relatively benign and only causes cutaneous lesions which are comparable with the lesions from parasite species causing cutaneous leishmaniasis (CL). Although some parasite-specific genes have been implicated in the visceralizing capacity of L. donovani, the associated phenotypic factors that are responsible for this change in tissue tropism are not well-understood. Past research already compared some phenotypic features, such as resistance to increasing temperatures and oxidative stress, between VL-causing L. donovani parasites and CL–causing L. major parasites. However, because of their evolutionary distance comparing different parasite species may not be completely correct as next to genetic variations, also phenotypic discrepancies unrelated to human pathology could be present. Therefore, this study aims at identifying the parasite-related phenotypic factors associated with visceralization by using two isogenetic strains. These will be created by phenotype-driven passive parasite selection from the target organs involved (skin vs. spleen) in the in vivo hamster model. After repeated selection of parasites with a specific tissue tropism and subsequent population enrichment, the course of infection with both the VL-causing and CLcausing parasites will be evaluated and compared by bioluminescence imaging. To characterize both parasite populations, the expression levels of A2, a virulence factor that has been associated with visceralization, will be compared and the strains will be characterized phenotypically in order to identify possible pitfalls during the visceralization process.

Researcher(s)

• Promoter: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project aims to improve current RSV vaccines, using glycan modifications of the RSV F protein to augment the capacity of the RSV F protein to induce neutralizing antibodies. This approach will be applicable in different types of vaccines, such as DNA vaccines, live attenuated vaccines, vector vaccines… Besides efficacy, evaluating of safety, and especially RSV vaccine-enhanced disease and mucus induction will be evaluated.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Leishmaniasis is a major neglected parasitic disease with a broad range of clinical manifestations including the lethal visceral disease. New drug discovery initiatives are essential given the serious adverse effects of current treatments and/or the increasing threat of drug resistance development. The present project aims to contribute towards novel concepts on intervention strategies that could bypass some problems relating to drug failure. Through the establishment of a sand fly colony, host-parasite interactions such as parasite virulence, disease-associated immunity and pathology, and treatment efficacy will be studied in laboratory rodent models that include the insect vector. The vector component will also allow improved antileishmanial lead characterization, drug resistance research and adaptation of clinical isolates to in vitro and in vivo laboratory models enabling improved monitoring of treatment efficacy in the field. This study will explore the interplay of host immune cells (neutrophils and monocytes) with recent clinical isolates and laboratory strains showing significant differences in virulence that arise from the acquisition of drug resistance. Responses will be studied by using a state-of-the art kinomics platform, that allows a straightforward acquisition of phenotypic fingerprints of intracellular kinase activation. This will provide cutting-edge information on the parasite-host interplay and on inflammation in general. Knowing that neutrophils have been ascribed infection-promoting activities, selective targeting of innate immune cell function will be explored as a complementary asset to control parasitic infections. This has not yet been explored, although anticipated to be much less prone to the development of resistance mechanisms. This approach could possibly also support the identification of novel drug or vaccine targets.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Human African trypanosomiasis (HAT) or sleeping sickness is a parasitic disease transmitted by tsetse flies with a relatively benign haemolymphatic followed by a lethal encephalitic stage. Treatment is increasingly compromised by emergence of drug resistance in addition to the known toxicity of current drugs. In response to this medical need, our previous hit-finding campaign identified nucleoside analogues that are highly potent and selective against trypanosomes in vitro and fully curative in vivo after oral administration (50 mg/kg for 5 days) in an acute mouse model. This project will make a structure-activity relationship by expanding two novel compound series to further optimize potency and to make drug uptake less dependent on a single transporter that is prone to resistance development. The chemical synthesis will be combined with detailed evaluation of compound efficacy using state-of-the art methodologies, including natural transmission models and in vivo bioluminescent imaging to assess overall impact of treatment. Aiming to comply with the desired target product profile for such drugs, potency will be evaluated in acute and chronic infections with cerebral involvement. Most promising compounds will be subjected to identification of the action mechanism using loss-of-function and protein biochemical approaches. Collectively, this project aims at providing a convincing proof-of-concept for the use of nucleoside analogues for the treatment of this neglected disease.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Neutrophils and macrophages are cells of the innate immune system of the mammalian host with a range of potential effector functions against pathogens. These cells are rapidly recruited to sites of parasite infection. Counterintuitively, neutrophils favor the onset of parasite infections as we have described for sleeping sickness parasites (Trypanosoma brucei sp.) inoculated by the bites of tsetse flies. Indeed, selective neutrophil removal or genetic conditions resulting in lower neutrophil levels in the blood yield a higher level of resistance to trypanosome infection. Monocytes on the other hand are activated to differentiate into activated macrophages that contribute to parasite control in the early stage of infection. The differential impact of neutrophils and macrophages suggests that specific inhibition of neutrophil functions could result in higher levels of resistance to infection. This project will compare the responses of neutrophils and monocytes to parasite presence by capturing their kinase activity fingerprints. Kinase targets in cell type specific and common responsive pathways will be identified. Kinase inhibitors from commercially available or proprietary collections will be used to selectively inhibit the parasite-induced responses and to evaluate the impact on parasite infection. Collectively, this project will forward our understanding of early trypanosome transmission and is directed at revealing novel transmission-blocking concepts and strategies.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

DNDi has screened a number of non-proprietary compounds that could potentially be used for the treatment of visceral leishmaniasis (VL). DNDi and research partners have further optimised these quality compounds to discover lead compounds or preclinical development candidates. DNDi and the research partners are interested in exploring the mechanisms of action (MOA) of these compounds with regard to Leishmania parasites and resistance (MOR) of the parasites to these compounds. The research will be conducted by the network of research collaborator(s) and may include in vitro and in vivo resistance selection, whole genome sequencing, metabolomics, genetic modification including up-and-down regulation, RIT-seq, PLATO, DiCRE, CISPR/Cas 9 and other applicable methods.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Sarah Hendrickx graduated with great distinction in 2010 in Biomedical Sciences at the University of Antwerp. Under the supervision of prof. Louis Maes at the Laboratory for Microbiology, Parasitology and Hygiene (LMPH), she performed her master thesis entitled 'Use of Leishmania reporter strains for in vitro and in vivo evaluation of antileishmanial drugs'. This way, she became actively involved in the ongoing research on the Leishmania parasite and encouraged her to pursue her research ambitions as a PhD student on an ongoing project at LMPH. After one year, she applied for and obtained the position of mandate assistant. Sarah became responsible for teaching several practical courses, such as 'Parasitology' (Biomedical Sciences and Veterinary Sciences); 'Immunochemistry and Cell Culture' (Biomedical Sciences) and 'Microbiology' (Veterinary Sciences). Despite these ample teaching activities and two maternity leaves, she finalized her PhD thesis, entitled "Emergence of drug resistance in visceral leishmaniasis treatment - Will paromomycin and miltefosine stand the test of time?" in December 2015. Her thesis focused on the emergence of resistance of the Leishmania parasite against all currently used antileishmanial drugs, highlighting the need to combat future emergence of resistance against the few remaining effective antileishmanials. She successfully applied for a FWO-postdoc position and a FWO-Krediet aan Navorsers to continue the work in visceral leishmaniasis in addition of establishing her own independent research line within LMPH with focus on the cutaneous variant of the disease that has not yet been covered at LMPH up until now. In order to obtain sufficient funding for this, she applied for an additional FWO-Krediet aan Navorsers earlier this year. Note: All the chapters of her PhD have been published in high impact international journals

Researcher(s)

• Promoter: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Neutrophils and macrophages are cells of the innate immune system of the mammalian host with a range of potential effector functions against pathogens. These cells are rapidly recruited to sites of parasite infection. Counterintuitively, neutrophils favor the onset of parasite infections as we have described for sleeping sickness parasites (Trypanosoma brucei sp.) inoculated by the bites of tsetse flies. Indeed, selective neutrophil removal or genetic conditions resulting in lower neutrophil levels in the blood yield a higher level of resistance to trypanosome infection. Monocytes on the other hand are activated to differentiate into M1 macrophages that contribute to parasite control in the early stage of infection. The differential impact of neutrophils and macrophages suggests that specific inhibition of neutrophil functions could result in higher levels of resistance to infection. This project will compare the responses of neutrophils and monocytes to parasite presence by capturing their kinase activity fingerprints. Kinase targets in cell type specific and common responsive pathways will be identified. Kinase inhibitors from commercially available or proprietary collections will be used to selectively inhibit the parasite-induced responses and to evaluate the impact on parasite infection. Collectively, this project will forward our understanding of early trypanosome transmission and is directed at revealing novel transmission-blocking concepts and strategies.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Mabille Dorien

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Treatment of tuberculosis is severely complicated by the adaptations of its etiological agent, Mycobacterium tuberculosis, allowing survival and replication within the host phagocytes. A better understanding of the host-pathogen interaction and the development of novel treatment strategies are thus critical. We strongly believe in a promising strategy involving the receptor-mediated delivery of therapeutics via the endocytic Sialoadhesin (Sn) receptor present on the surface of phagocytes.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Caljon Guy
• Co-promoter: Delputte Peter
• Fellow: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project is a continuation of a former project that focused on the in depth evaluation of novel benzodiazepine antifungal compounds that proved to be highly active against dermatophyte infections. However, when focusing on the medical needs in the field, onychomycosis remains the sole infection within the broader group of dermatomycoses that could represent a market potential. This project specifically focuses on the potential of the preferred hit compound in a onychomycosis model with particular focus on model development and permeation characteristics through the nail after topical administration and in the nail bed after oral administration.

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project specifically envisages undertaking protocol optimizations towards implementation of an RNA-based Leishmania detection method in the post-treatment follow-up of visceral Leishmaniasis patients in upcoming clinical studies in Kenya. The optimization will take into account typical issues encountered in a (tropical) field settings.

Researcher(s)

• Promoter: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract. The aim of the project is to set-up a center of scientific excellence in the Central-Eastern region of Cuba for traditionally used bioactive plants and their metabolites.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: De Winter Hans
• Co-promoter: Pieters Luc

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand DNDI. UA provides DNDI research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

According to ECDC, over 4 million healthcare-associated infections in the EU cause 37,000 deaths and cost EUR 7 billion/year. Half of them are related to medical devices (i.e., catheters, implants) and 80% of these are related to bacterial biofilms. A recent EC report highlighted the medical device sector's role in driving EU economic growth, employing 500k people in 25k companies (80% are SMEs) with annual sales of EUR 85 billion. The strategy to prevent medical device-infections is alteration of the device's surface with antimicrobials. However, current antimicrobial surfaces don't control bacterial growth in tissue surrounding implants, and only Sterilex® has received regulatory approval in the US as anti-biofilm agent. Participants in this proposal have earlier demonstrated a dramatic in vitro inhibition of biofilm formation by 3D-printing surfaces with antibiotics incorporated into the carrier polymers. This discovery opens new possibilities for printed medical devices that better resist biofilms. Our objective is to setup a new European education platform to guide and inspire young researchers in the intersectoral exploration of innovative routes to counteract microbial biofilms by fabricating anti-infective, tailored, 3D-printed medical devices. Current opportunities for young researchers to receive an structured, inter-sectoral and up-to-date education on personalized medicine and medical devices are marginal, and to our knowledge PRINT-AID is the first ETN set up for this purpose. State-of-the-art printing technologies will be combined with in vitro and in vivo biofilm models and novel tools for data integration/standardization. Doctoral training will be performed within a high-quality network of 12 participants (5 industrial) from the EU and US. It will include online and face-to-face courses taught by researchers with academic and industrial expertise in biofilms, 3D-printing research, antimicrobials, material science, and drug development.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Antibiotics have revolutionized medical practice against life-threatening infectious diseases. However, the evolution of antibiotic resistance currently poses a major threat to health-care, leading to worldwide increased morbidity and mortality. In addition to resistance, it is becoming clear that antibiotic therapy failure in many bacteria also results from a subset of cells that have switched to an antibiotic-tolerant "persister" state. Indeed, the survival of an antibiotic-sensitive bacterial population challenged with the lethal activity of antibiotics critically depends on the presence of this small fraction of non-growing, transiently antibiotic-tolerant cells. A recent study demonstrates that Escherichia coli persister levels can be very quickly tuned to the frequency of previous antibiotic encounters by genetic adaptation, leading to extreme levels of multidrug tolerant persisters when applying antibiotics daily. A similar rapid evolution of persistence was demonstrated in many important bacterial pathogens including urinary pathogenic E. coli and Burkholderia. Together, these results indicate that bacteria can genetically store information of past antibiotic treatments. We hypothesize that a similar evolutionary process may occur in vivo, thereby impeding successful clearance of the bacteria from the host. We will test this hypothesis by performing in vivo evolution experiments using urinary tract and lung infection models in mice.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Amphotericin B (AmB) is currently implemented as first-line treatment for visceral leishmaniasis (VL) in large parts of the world, while the use of miltefosine (MIL) is endorsed as second option, either in mono- or in combination therapy. However, a cumulative number of treatment failures is being reported, necessitating repeated treatments that may obviously facilitate emergence of resistance. As isolates from clinical relapse patients still demonstrate a 'drug susceptible' phenotype, factors other than intrinsic drug resistance may likely influence treatment outcome. Next to some phenotypic parasite traits, such as infectivity and multiplication potential, treatment failure has also been linked to a decreased drug exposure in particular parasite niches, such as in liver granulomas preventing sterile cure upon drug exposure. In this project, the complex interplay between the parasite's (epi-)phenotype, the drug and the host's immune reaction will be explored using syngeneic VL strains derived from a cure, relapse and resistant background. The impact of the development of granulomas upon infection with the different strains will be compared in relation to the in vitro and in vivo drug efficacy and relapse potential.

Researcher(s)

• Promoter: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Neutrophils and macrophages are cells of the innate immune system of the mammalian host with a range of potential effector functions against pathogens. These cells are rapidly recruited to sites of parasite infection. Counterintuitively, neutrophils favor the onset of parasite infections as we have described for sleeping sickness parasites (Trypanosoma brucei sp.) inoculated by the bites of tsetse flies. Indeed, selective neutrophil removal or genetic conditions resulting in lower neutrophil levels in the blood yield a higher level of resistance to trypanosome infection. Monocytes on the other hand are activated to differentiate into M1 macrophages that contribute to parasite control in the early stage of infection. The differential impact of neutrophils and macrophages suggests that specific inhibition of neutrophil functions could result in higher levels of resistance to infection. This project will compare the responses of neutrophils and monocytes to parasite presence by capturing their kinase activity fingerprints. Kinase targets in cell type specific and common responsive pathways will be identified. Kinase inhibitors from commercially available or proprietary collections will be used to selectively inhibit the parasite-induced responses and to evaluate the impact on parasite infection. Collectively, this project will forward our understanding of early trypanosome transmission and is directed at revealing novel transmission-blocking concepts and strategies.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Mabille Dorien

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are able to survive inside macrophages. Miltefosine (MIL) is an oral drug used to treat VL patients but is increasingly failing to permanently clear parasites from the patient. Parasites from these relapse patients do not seem to display an increased resistance to the drug but are able to modify the immune system to promote survival inside macrophages even in conditions where the drug is administered. The impact of drug treatment on parasite survival will be evaluated in various tissues using molecular and imaging technologies in rodent models of VL following a natural parasite transmission. Recently, two syngeneic strains of L. infantum were selected with different levels of sensitivity to MIL-treatment in vivo. The resistant strain (and its sensitive counterpart) was made bioluminescent by introduction of the luciferase enzyme (PpyRE9). The use of bioluminescence imaging (BLI) allows the non-invasive evaluation of the parasite burden and distribution in various tissues and allows assessing the impact of MIL-treatment in vivo. The transgenic parasites will additionally be provided with a fluorescent marker (DsRed or TagGFP2) for detecting parasites by flow cytometry. This project aims to gain insights into the multifactorial causes of MIL-therapy failure and will focus specifically on the impact of the activation state of Kupffer cells (KC) and the recruitment of neutrophils. Infection with the two transgenic parasite lines will be followed by in vivo imaging in (i) KC-reporter (Clec4f-YFP DTR) mice in which KCs can be detected and enriched through their YFP signal and (ii) Genista mice in which a recessive mutation is responsible for a neutropenic condition with absence of mature neutrophils. This approach will allow to gain insights into the cell-based immunological basis of treatment failure. By transcriptional studies, this study will also allow us to identify the involved immunological pathways and potentially allow the design of host-directed therapies to reduce the risk of relapse. The multidisciplinary approach will lead to new insights into the complex interactions between the parasite, the host and the drug and will allow the formulation of recommendations for treatment against VL.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Bulté Dimitri

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Amphotericin B (AmB) is currently implemented as first-line treatment for visceral leishmaniasis (VL) in large parts of the world, while the use of miltefosine (MIL) is endorsed as second option, either in mono- or in combination therapy. However, a cumulative number of treatment failures is being reported, requiring the need for repeated treatments that will facilitate emergence of resistance. As isolates from clinical relapse patients generally still demonstrate a 'drug susceptible' phenotype, factors other than intrinsic drug resistance may likely influence treatment outcome. For MIL, increased infectivity and metacyclogenesis potential of the infecting parasites has been suggested, while preliminary observations from our laboratory indicate similarities for AmB. Treatment failure has also been linked to a decreased drug exposure in particular parasite niches, such as in liver granulomas precluding sterile cure upon drug exposure. In this project, the complex interplay between the parasite's (epi-)phenotype, the drug and the host's immune system will be explored using syngeneic VL strains derived from a cure, relapse and resistant background. More in particular, virulence will be compared in the sand fly vector and in in vitro and in vivo laboratory models. The impact of the development of granulomas upon infection with the different strains will be compared in relation to the in vitro and in vivo drug efficacy and relapse potential.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Caljon Guy
• Fellow: Hendrickx Sarah

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) or Kala-Azar is a neglected tropical disease caused by Leishmania parasites that are able to survive inside macrophages. Miltefosine is an oral drug used to treat VL patients but is increasingly failing to permanently clear parasites from the patient. Parasites from these relapse patients do not seem to display an increased resistance to the drug but are able to modify the immune system to promote survival inside macrophages even in conditions where the drug is administered. The impact of drug treatment on parasite survival will be evaluated in various tissues using molecular and imaging technologies in rodent models of VL following a natural parasite transmission. Combination of this information with the quantification of drug levels in these tissues, will allow to pinpoint in which tissues parasites are most likely to survive drug treatment. The expression of genes following infection and drug treatment will be analyzed inside infected liver macrophages (Kupffer cells, KCs) in order to understand how parasites from relapsed patients can survive inside host cells. Using transgenic mouse models, this research will allow to evaluate the impact of KCs and KC gene expression on infection and treatment outcome. Collectively, the proposed multidisciplinary approach will improve our understanding of the complex interactions between the parasite, its host and the drug and will allow the formulation of recommendations for improved treatment interventions.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Van Bockstal Lieselotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Our research focuses on resistance against the only oral drug miltefosine and will provide novel data to the field. Our results will not only be important to the parasitology field, but also to clinicians and public health professionals, supporting clinical decisions on future treatment policies, adequate diagnostic approaches and epidemiological resistance monitoring.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Maes Louis
• Fellow: Eberhardt Eline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Octahydrobenzo[j]phenanthridinediones (OQDs) have found to be potent antitubercular compounds with Minimal Inhibitory Concentrations (MICs) as low as 0.22 μM against both drug susceptible Mycobacterium tuberculosis (Mtb) and multi-drug resistant Mtb. Moreover, for the ester analogs we have reported a selectivity index value (CC50/MIC) of nearly 200. In the Mtb-BALB/c mice infection model, treatment of Mtb aerosol infected mice with 25 mg/kg of the lead compound reduced the bacterial load by 99%. Preliminary results have indicated that the OQDs presumably interfere with the bacillary redox homeostasis and provoke an increase in the intracellular reactive oxygen levels. The putative target for quinone analogues, according to literature, although disputed, could be mycothione reductase (Mtr). The Mtr enzyme controls the intracellular reductive environment by maintaining the low molecular thiol couple, mycothione/mycothiol, that functions as the prominent redox couple in Mtb in its reduced form. In the envisaged mechanism of action of the OQDs, the compounds act as redox cyclers with Mtr, abrogating its function. In addition, the reaction of the OQDs with Mtr results in an array of free radicals to which the bacillus ultimately succumbs. As the bacillary redox homeostasis is an unexploited target, the OQDs could be used to study the Mtr as an innovative strategy for the generation of novel mycobacteriocidal compounds. In this part of the project we want to investigate how the OQDs' activity is mediated. To this extend cell free models will be created in which the putative target is recombinant expressed and the affinity with the compounds will be confirmed. Furthermore we aim to explore the redox status within both the host cell, the macrophage, as in the bacillus itself, following exposure with the OQDs compounds. This research will greatly improve our understanding in the mechanism of action of the OQDs, the bacillary redox homeostasis and could provide the necessary proof of concept for the generation of novel anti-tubercular compounds in the long run.

Researcher(s)

• Promoter: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The BOFZAP research is aimed at understanding the cellular and molecular immunological basis of host tissue colonization by parasite and treatment failure in experimental models of leishmaniasis and trypanosomiasis.

Researcher(s)

• Promoter: Caljon Guy
• Fellow: Caljon Guy

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A strong anti-mycobacterial activity was found for a group of symmetrically substituted 1,3-diaryltriazenes. The compounds did not show genotoxicity and mutagenicity and the anti-mycobacterial activity was dependent on the substitution pattern. In this project we want to investigate (i) how the current lead compound can be optimized, (ii) if the compounds fulfill the WHO criteria and (iii) what the mechanism of action is of the 1,3-diaryltriazenes.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Cappoen Davie
• Fellow: Torfs Eveline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

For many viruses, efficient vaccines and/or antivirals are in use. Yet, for some viruses, vacccines/antivirals only provide limited protection, or fail because of induction of resistance, or are simply lacking because of a lack of fundamental knowledge. Since these products are crucial to control virus replication and virus-induced disease, we propose a programme of fundamental research to gather new insights in some crucial aspects of the pathogenesis of viral diseases, which should allow development of future vaccines and antivirals.

Researcher(s)

• Promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral Leishmaniasis (VL) is the most deadly disease outcome of various forms of leishmaniasis and is caused by either L. donovani or L. infantum. First-line treatment still mainly relies on pentavalent antimonials, but drug resistance in both species is increasingly posing a threat to disease control. Miltefosine (MIL) has recently become available as first-line back-up drug, however, increased rates of treatment failure and relapses are now being reported in disease endemic areas, suggesting the emergence of drug resistance. To date, no optimal laboratory model exists to study the full impact of MIL resistance development as no resistant field strains could yet be identified in the laboratory. Mechanisms of drug resistance are most often studied in in vitro settings in which the parasite (generally promastigote stage) is directly exposed to a particular drug. At the University of Antwerp, the Laboratory for Microbiology, Parasitology and Hygiene (LMPH) developed a new in vitro assay on intracellular amastigotes to induce drug resistance while aspects of host-parasite interactions such as virulence (infectivity and fitness) and disease associated pathology are studied in laboratory rodent models. Both clinical field isolates and well-established laboratory parasite strains are used to assess dynamics and mechanism(s) of MIL resistance development, in parallel to in vivo virulence development and assessment of treatment relapse.

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This DnDi funded project relates to the preclinical evaluation of lead compounds with anti-parasitic activity for treatment of Leishmaniasis, Chagas disease and African trypanosomiasis. Compounds are also evaluated for cytotoxicity.

Researcher(s)

• Promoter: Caljon Guy
• Co-promoter: Cos Paul
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Respiratory Syncytial Virus (RSV) is the leading cause of severe lower respiratory disease in young children and is the second most important viral cause of respiratory disease in adulthood, after influenza virus. Currently, no vaccines and no antivirals are available to control RSV infections. Recent advances in RSV research have shown that the F protein is a major target for development of novel therapy and prophylaxis. F-specific antibodies, such as Palivizumab, are available, but were shown not to be fully effective, since hospitalization rates are reduced only by 55%. In addition, vaccines may also not fully protect against infection. This is exemplified by the fact that even after natural infection(s) and induction of F-specific neutralizing antibodies, RSV is able to reinfect. Since re-infection occurs without considerable antigenic change, there must be a different immune evasive mechanism than that influenza A virus reinfections, which is dependent on antigenic drift/shift. Our understanding of RSV F protein functionality, besides its role in fusion, is however insufficient to explain the immune evasive mechanisms involved. Currently there is a great risk that newly developed monoclonal antibodies and vaccines will suffer from constrained effectiveness. Very recently, preliminary studies in our research group have shown that upon binding of RSV-specific antibodies to RSV F protein expressed on the surface of infected cells, internalization occurs of RSV protein-antibody complexes. As a result, infected cells will most likely no longer be efficiently detected and eliminated by antibody-based immunity. In addition, a reduction in the expression of RSV proteins on the surface of infected cells may interfere with the immunogenicity and hamper the induction of strong immune responses. This novel finding may have profound effects on (1) our understanding of RSV pathogenesis and the occurrence of frequent RSV reinfections and (2) the development of new RSV vaccines and monoclonal antibodies. It is therefore the aim of this project to fully characterize this endocytosis process up to the molecular level, both in vitro and in vivo. We will (A) characterize the endocytic process and the consequences for RSV immune evasion, (B) identify amino acids of the F protein involved and create F proteins that show no internalization, (C) generate recombinant viruses with mutant F proteins lacking endocytic properties and (D) evaluate the recombinant viruses in vivo.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Maes Louis
• Fellow: Van der Gucht Winke

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

RSV is worldwide an important cause of medical relevant lung infections, which can lead to life-threatening bronchiolitis in children and elderly. Besides the acute pathology, there is a link between severe bronchiolitis and chronic respiratory problems. The pathology is induced by both the cytopathic effect of the infection as well as the RSV induced immunomodulation. Since immune cells are an important component, we will study the interaction of RSV with these cells and try to modulate their activities.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Heykers Annick

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Pannus Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

(Mtb) are in high demand. In a past FWO project (G0020.10N) we synthesized and identified the class of octahydrobenzo[j]phenanthridinediones as promising antitubercular drug candidates. Ester analogs of the compound class showed a high degree of selectivity. For these compounds, we observed a sub-μM minimal inhibitory concentration against Mtb nearly 200 times lower than the 50% cytotoxic concentration against eukaryotic cells. However, the mechanism of action and the basis of selectivity remain unknown. Therefore, the general objective of this project is to study the mechanism of action of the octahydrobenzo[j]phenanthridinediones. We hypothesize a selective inhibition of mycothione reductase, a unique redox pathway in Actinobacteria, as the action mechanism. To this end,(i) we will identify the proposed target through genomic analysis of spontaneous Mtb mutants.(ii) We will validate the identified target through enzymatic and cellular approaches. (iii) In addition, we will study the activity against metabolically inactive bacilli and the synergism with existing TB drugs using state of the art models. This study will contribute to the fundamental understanding of the mechanism of action of the compound class and will add to the common knowledge on mycobacterial mycothione reductase. In the long term, the gathered knowledge could add to the development of new antitubercular drugs.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Abbaspour Tehrani Kourosch
• Fellow: Cappoen Davie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Our research focuses on resistance against the only oral drug miltefosine and will provide novel data to the field. Our results will not only be important to the parasitology field, but also to clinicians and public health professionals, supporting clinical decisions on future treatment policies, adequate diagnostic approaches and epidemiological resistance monitoring.

Researcher(s)

• Promoter: Caljon Guy
• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Maes Louis
• Fellow: Eberhardt Eline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Hercules Foundation. UA provides the Hercules Foundation research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Delputte Peter
• Co-promoter: De Meyer Guido
• Co-promoter: Dewilde Sylvia
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Lebeer Sarah
• Co-promoter: Leroy Jo
• Co-promoter: Van Cruchten Steven
• Co-promoter: Wenseleers Wim

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). It will establish a drug discovery platform, PDE4NPD, that combines phenotypic screening with efficient target-centric drug discovery, including target validation, various strategies for compound screening, PDE hit and lead optimization, safety and toxicology assessments and evaluation of anti-parasitic activity.

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between UA and CAPES (Brasil). UA provides CAPES research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Miltefosine (MIL) was recently positioned as first-line therapy for visceral leishmaniasis. Its long half-life and low adherence could promote resistance. To safeguard MIL-efficacy, resistance mechanisms and their cell biological and clinical implications should be studied proactively. This study aims to experimentally induce MIL-resistance to assess the effect of resistance on MIL-uptake and parasite-macrophage interaction.

Researcher(s)

• Promoter: Boulet Gaëlle

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The general aim of this project is the design of an improved mRNA platform in order to enhance both the strength and the breadth of HIV-1 Gag-specific T cells. To this end, we will develop strategies that act to increase antigen translation and Tcell co-stimulation on the one hand, and on the other hand to improve antigenic coverage. Taken together, these approaches will result in a superior mRNA vaccine that could ultimately develop into a universal immunotherapy against HIV-1.

Researcher(s)

• Promoter: Vanham Guido

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis, itself the commonest single cause of hospitalization during infancy. In older children and in adults, RSV is associated with acute exacerbations of both asthma and chronic obstructive pulmonary disease (COPD). Following the infection of ciliated epithelial cells, the manifestations of bronchiolitis are caused by a combination of viral cytotoxicity and the uncontrolled immune response to infection.

Researcher(s)

• Promoter: Delputte Peter
• Fellow: Leemans Annelies

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Ocular Surface diseases (OSD) such as dry eye syndrome (DES) show an estimated prevalence between 15 and 29%. The only FDA approved and on subscription dry-eye treatment is cyclosporine 0.05% (Restasis®), but this formulation is not available in the EU. Novel therapies for OSD are therefore needed. The expertise within ADDN fosters a unique opportunity to set up a preclinical platform on OSD leading to an increased collaboration with industrial partners.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen
• Co-promoter: De Meester Ingrid
• Co-promoter: Joossens Jurgen
• Co-promoter: Kiekens Filip
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The goal of this project is to characterize this novel phenotype and to develop the tools to allow us to routinely etect 'stealth' amastigotes. This wil be done by developing monoclonal antibodies that can discriminate 'stealth' from regular amastigotes using immunofluorescent stainings and to evaluate differential gene expression between 'stealth' and regular amastigotes in macrophages.

Researcher(s)

• Promoter: Boulet Gaëlle

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Increasing resistance of Mycobacterium tuberculosis to antibiotics plays a crucial role in the current epidemiology of tuberculosis (TB). Because of, amongst others, inadequate treatment of multi-drug resistant (MDR) TB - with resistance to isoniazid and rifampicin - the incidence of extreme-drug resistant (XDR) TB - defined as MDR-TB with additional resistance to fluoroquinolones (FQ) and one of the injectable second-line antibiotics - worldwide. Clinical studies show that the use of FQs is necessary for successful MDR-TB treatment. Clofazimin (CLOF) is also being used more and more in the standard treatment of MDR-TB. Clinical CLOF-resistant M. tuberculosis isolates have been poorly described to date and the resistance mechanisms are insufficiently known. It is suspected that CLOF provides an increased release of lysophospholipids on the one hand and superoxide and hydrogen peroxide on the other, resulting in bacterial cell death. The molecular mechanism behind the potential effect of CLOF is not well known, but efflux pumps may play a role in resistance. The proposed study aims to identify new resistance mechanisms for two antibiotics that form the pillars of MDR-TB treatment.

Researcher(s)

• Promoter: Rigouts Leen
• Fellow: Coeck Nele

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project aims to identify new mechanisms for the modulation of macrophages during activation of the immune system and during pathogen infections, using sialoadhesin, a macrophage-specific surface protein.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Cos Paul
• Fellow: De Schryver Marjorie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis (VL) is caused by Leishmania donovani and L. infantum. Current drug therapies are associated with resistance, a high cost price, parenteral administration or serious side effects. Miltefosine (MIL) is the first oral drug against VL with a good therapeutic effect and ease of use and an acceptable safety profile. Recently, MIL was positioned as first-line therapy in India, Nepal and Bangladesh. However, MIL shows some characteristics that promote the emergence of resistance. The selection of MIL-resistant strains should be prevented and monitored, especially since there are no alternative drugs in clinical development. To proactively address the development of MIL-resistance, research on the resistance mechanisms and their cell biological and clinical implications is very important. This research project aims to obtain a standardized, clinically relevant laboratory model for the experimental induction of MIL-resistance. The MIL-resistant strains will be used to evaluate the effect of resistance on the MIL-uptake and parasite-cell interaction in Leishmania-infected macrophages. In addition, the fitness of the resistant strains will be assessed.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Fellow: Mondelaers Annelies

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the other hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In this research project we will be investigating fundamental aspects related to the action of antibiotics against biofilms. In addition, in the long term our results could lead to the rational development of non-toxic agents that reduce the ability of biofilm cells to deal with ROS-related stress and could be used in combination with conventional bactericidal antibiotics.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Van Assche Tim

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Van kerckhoven Marian

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A recent study of our group indicated that it is safe to immunize HIV-1 infected patients with dendritic cells (DC) loaded with mRNA encoding subtype B consensus Gag or chimeric Tat-Rev-Nef. An increase in the antiviral cellular immune responses was observed. The aim of this project is to further optimize the DC vaccination strategy. This will be done using: - A more stable mRNA, - An antigen or combination of antigens to induce immune responses directed at different variants worldwide - Co-stimulatory signals to improve the DC immunogenicity.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Bracke Lotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The primary research aims of this project proposal are to unravel the dynamics and mechanisms of PMM and MIL resistance in L. donovani and L. infantum. To this end, our novel in vitro method for induction of drug resistance in amastigotes will enable to explore several aspects of PMM and MIL resistance prior to their routine use in the field. The deliverables of our study will contribute to the implementation of strategies/policies to avoid the appearance of drug resistance and assure the long-term efficacy of MIL and PMM.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Paulussen Caroline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Goovaerts Odin

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Rigouts Leen
• Fellow: Coeck Nele

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand DNDI. UA provides DNDI research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The aim of this research community is to better understand the formation and the structure of bacterial and fungal biofilms in humans. This could lead to a more efficient treatment of biofilm-related infections.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Bacterial isolates from intensive care unit patients will be collected from urinary and intravascular catheters and endotracheal tubes. The biofilm phenotype in relation to antibiotic treatment failure will be investigated using molecular biological, bio-imaging techniques and in vitro and in vivo biofilm models. Particular emphasis will be given to Escherichia coli for urinary tract infections (UTI), Pseudomonas aeruginosa for ventilation associated pneumonia (VAP) and Staphylococcus aureus for systemic infections related to venous catheters. The acquired library of fully typed strains will enable in depth study of putative virulence factors that contribute to biofilm formation and treatment failure.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Dewilde Sylvia
• Co-promoter: Goossens Herman
• Co-promoter: Malhotra Surbhi

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Cos Paul
• Fellow: Clais Sofie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Dafra. UA provides Dafra research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: De Haes Winni

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A recent study of our group indicated that it is safe to immunize HIV-1 infected patients with dendritic cells (DC) loaded with mRNA encoding subtype B consensus Gag or chimeric Tat-Rev-Nef. An increase in the antiviral cellular immune responses was observed. The aim of this project is to further optimize the DC vaccination strategy. This will be done using: - A more stable mRNA, - An antigen or combination of antigens to induce immune responses directed at different variants worldwide - Co-stimulatory signals to improve the DC immunogenicity.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Bracke Lotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Biofilm-related infections prove exceedingly difficult to treat because the organisms in a biofilm are protected from the circulating antimicrobials. Up till now, there have been relatively few studies investigating biofilm development in clinical isolates. Current in vitro methods for studying microbial adhesion and growth on biomaterial surfaces lack the influence of the host immune system, endorsing the specific need for animal models that allow temporal and spatial measurements based on non-invasive bio-imaging techniques using reporter strains. To improve our ability to prevent and/or treat biofilms, we need a better understanding of their formation and persistence. The specific goals of this research proposal are to i) understand the physiology of mono- and polymicrobial biofilms, with focus on staphylococci and Candida spp., isolated from indwelling devices from ICU patients and ii) implement in vitro and in vivo laboratory biofilm models that adequately reflect the real-life situation.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Goossens Herman
• Co-promoter: Maes Louis
• Co-promoter: Malhotra Surbhi
• Fellow: Kerstens Monique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Paulussen Caroline

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Vanaerschot Manu

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Goovaerts Odin

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Determination of drug susceptibility of Leishmania strains isolated from HIV co-infected patients using a combined approach of biological in vitro susceptibility testing (LMPH) and molecular biology tools.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project focuses on some fundamental biological characteristics of an infection with the parasitic protozoa Giardia intestinalis, more in particular: 1/ mucosal interactions between the parasite and the host using in vitro and in vivo models and 2/ intestinal pathogenetic factors (virulence, infalmmation, motility, e.a.) that will affect the clinical outcome of the infection.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Fellow: Bénéré Ely

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

As the number of HIV-1 infections worldwide is still rising, there is an urgent need for microbicides which are vaginal formulations used by women to prevent heterosexual HIV transmission. Within this project, inhibitors of HIV-1 reverse transcription, integration and entry are evaluated as potential microbicides in vitro.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Selhorst Philippe

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The goal of this project is to gain insight in the role and applicability of virulence inhibitors in bacterial infections. The objectives are: 1. Development of an in vitro multi-species biofilm model with P.gingivalis. 2. Development of an in vitro virulence model for P. gingivalis-mediated collagen degradation. 3. Development of P.gingivalis animal model. 4. Evaluation of virulence inhibitors in bacterial in vitro and in vivo models.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The goal of this project is to gain insight in the role and applicability of protease (DPP4) inhibitors in bacterial infections. The proof-of-concept will be obtained in Porphyromonas gingivalis models with the following objectives and work packages: 1. Development of in vitro and in vivo virulence models for P. gingivalis. 2. Evaluation of enzyme inhibitors using purified recombinant P. gingivalis DPP4. 3. Evaluation of DPP/protease inhibitors in bacterial in vitro and in vivo models. 4. SAR and optimisation of the lead compounds. 5. Biochemical characterisation of lead compound-target enzyme interactions.

Researcher(s)

• Promoter: Cos Paul
• Co-promoter: Augustyns Koen
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Maes Louis
• Co-promoter: Van Der Veken Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

We aim to increase the immunogenicity of the HIV envelope by generating CD4-independent viruses and by inducing resistance to entry and fusion inhibitors. The working hypothesis is that in this way we force the virus to adopt a more open conformation, resulting in the exposure of more conserved regions of Env, which should facilitate the induction of broad cross-neutralizing antibodies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Grupping Katrijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Vanham Guido
• Fellow: De Haes Winni

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This EU-FP7 multi-disciplinary project, named KALADRUG-R, aims to develop, evaluate and disseminate new tools for evaluation of drug resistance in L. donovani as well as innovative methodologies for monitoring Kala-Azar treatment effectiveness under field conditions. The UA is specifically involved in basic research related to oxidative stress sensitivity to antimony-resistant strains and in applied research related to phenotypic evaluation of drug resistance in laboratory models. This involves in vitro growth end metacyclogenesis of promastigotes of field isolates and sensitivity evaluation at the level of intracellular amastigotes. The fitness profile of these field strains will be assessed in laboratory animal models.

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The specific objectives of this research proposal are: ¿ Optimisation and validation of EPR analysis for ex vivo quantification and identification of free radicals in macrophages. ¿ Determining the role of oxidative stress in the survival of the Leishmania parasite in the macrophage. ¿ Studying the link between oxidative stress and the action of current (antimonials) and new (PX-6518) antileishmanial compounds.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The objective of the research is to obtain a series of well characterized fractions enriched in MFGM-glycoproteins with a high potential for anti-H.pylori action, due to their anti-adhesion and/or antimicrobial effects. In addition, these fractions will be checked for resistance towards gastro-intestinal digestion, and, in case of low digestibility, for possible effects on the composition and bioactivity of the microbiota in the large intestine.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Maes Louis
• Fellow: Vanaerschot Manu

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The search for a HIV vaccine, able to induce broad cross-neutralizing antibodies (BCNA) remains a top priority. BCNA can be found in a minority of chronically HIV-infected subjects. Based on their plasma, we will select the responsible epitopes, based o, a "peptide phage display" method. On the other hand, we have at our disposal several "antibody phage libraries", based on the bone marrow of patients with BCNA. Therefore, it will be possible to isolate new BCNA via the previously selected peptides. Possible applications include the development of a multi-component vaccine and therapeutic antibodies

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Dieltjens Tessa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to better understand the mechanisms of HIV transmission in the female genital tract by the development of an "in vitro dual chamber model". In the apical chamber, various epithelial cell lines, representative of the different compartments of the female genital tract, are grown to confluence on a semi-permeable membrane. In the basal chamber primary target cells, including macrophages, dendritic cells and T cells, are present. In this system, we can check which are the determinants of transmission of both cell-free and cell-associated HIV and we can also investigate how to block transmission of course. The latter is important in the development of new preventive stategies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Gali Youssef

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project focuses on some fundamental biological characteristics of an infection with the parasitic protozoa Giardia intestinalis, more in particular: 1/ mucosal interactions between the parasite and the host using in vitro and in vivo models and 2/ intestinal pathogenetic factors (virulence, infalmmation, motility, e.a.) that will affect the clinical outcome of the infection.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Bénéré Ely

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The proposed PhD projects fits into the development of immunotherapy with dendritic cells in HIV-infected subjects under highly active anti-retroviral therapy (HAART). The specific aims are the following: 1)Define the correlates of protective T cell immunity in "secondary controllers", subjects who suppress HIV after stopping HAART. 2)In vitro induction of protective responses, based on co-cultures of T cells and dendritic cells (DC), transfected with mRNA encoding autologous HIV proteins 3)In vivo evaluation of safety and immunogenicity of DC in a SIV macaques model and in a phase 1 study of patients under HAART

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Selhorst Philippe

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The project contains field research in the context of the ongoing activity profiling of PX-6518 against cutaneous Leishmania species. Primary objectives are to obtain insight and experience in New-World leishmaniasis and to transfer validated in vitro laboratory Leishmania models between the North and the South partner. The action of the new antileishmania lead compound PX-6518 against recently collected Peruvian field CL-strains will be further studied within a collaboration between the UA-LMPH and the University at Lima, Peru.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand ITG. UA provides ITG research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Coosemans Marc

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand ITG. UA provides ITG research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Coosemans Marc
• Fellow: Versteirt Veerle

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to contribute to the development of anti-HIV drugs that could be used preventively in a vaginal application by women. A number of candidate-microbicides has been proposed in a European program, which also provides a PhD scholarship to Katty Terrazas. It is our task to test the candidates in an in vitro model, using primary dendritic cells and T cells. Products with a favorable therapeutic index will be tested for synergism. In addition we want to avoid cross-resistance with therapeutic drugs.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Terrazas Aranda Katty

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

One of the main challenges ahead for the design of an effective HIV vaccine is the definition of true correlates of immune protection against HIV infection. Although it is still controversial which immune responses, humoral or cellular are most important in protection against infection, both types have been shown to contribute. Currently used ex vivo assays to measure anti-HIV cellular immune responses assess the immune response against a small part of the HIV virus, whereas for initial screening it would be more appropriate to increase the sensitivity of the assay as much as possible. Overlapping peptides are widely used but require a lot of cells and would be better used at a second or subsequent line. The use of infectious virus requires a level 3 security lab whereas inactivated virus would not be able to adequately monitor CD8+ T cell responses due to the lack of endogenous antigen presentation. Previous studies have succeeded to circumvent this difficulty by using single-cycle HIV-1 as stimulating antigens to stimulate HIV-specific CD4+ and CD8+ T cell responses. HIV pseudoviruses particles have been designed and are currently used to monitor in vitro virus neutralisation and the efficacy of potential anti-HIV drugs. This project aims to construct subtype-specific HIV-1 pseudoviruses as a source of HIV antigens as a first line screening assay to broadly monitor HIV-specific cellular immune responses in vitro. In order to stimulate HIV-specific cellular immune responses against a maximum of HIV-1 epitopes via MHC class I and II pathway, we want to construct HIV-1 pseudoviruses that contain all HIV-1 proteins as well as a pseudoviral genome that encodes for all HIV-1 proteins. The three main objectives of this project are: 1.Development of a technology to construct subtype-specific HIV-1 pseudoviruses, which can be used to present all HIV-1 antigens though natural antigen processing. 2.To compare the cellular immune responses measured with HIV-1 pseudoviruses with those responses measured with overlapping HIV-1 peptides, recombinant proteins and recombinant vaccinia viruses. 3.To assess correlations between cellular immune responses measured with HIV-1 pseudoviruses correlate with disease progression or protection against infection with HIV.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Beels Dominique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Visceral leishmaniasis (VL) is a tropical parasitic disease due to infection with Leishmania (Leishmania) infantum or Leishmania (Leishmania) donovani that primarily affects the liver, the spleen and the bone marrow. Worldwide, antimonials are the first line treatment of VL, but in some regions, as North-East India and the bordering regions in Nepal, treatment failure due to the parasite has emerged and seems to be spreading. This project will contribute to a better understanding of (i) the interaction between Leishmania and its host cell, the macrophage, (ii) the action mechanism of antimonials, (iii) in vitro resistance of Leishmania to antimonials and (iv) the in vivo treatment failure. Eventually, we hope to identify a molecular marker of treatment failure of antimonials to be able to efficiently follow up the emergence and further spreading of parasites causing treatment failure, what is of the greatest importance for setting up and evaluating control measures.

Researcher(s)

• Promoter: Maes Louis
• Fellow: Vanaerschot Manu

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Coosemans Marc
• Fellow: Herreman Christiane

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A new research initiative will study the micro-aerophilic intestinal protozoa Giardia intestinalis. This pathogen has developed anti-oxidative defense mechanisms to withstand the oxygen tension in tissues and organs, e.g. via oxidation of cellular thiols, superoxide-dismutase and possibly other mechanisms. The importance of these mechanisms is illustrated by the fact that current therapeutics (nitro-compounds) exert their action via selective increase of oxidative stress. The research plan involves the following steps: 1. development/optimization of in vitro culture method for trophozoites 2. establishment of conditions for induction of cyst formation, 3. development of a suitable laboratory animal model, 4. influence of oxidative stress on the in vitro and in vivo survival by in situ quantification of oxidative/antioxidative phenomena 5. evaluation of new molecules in the in vitro and in vivo models 6. evaluation of disinfectants for inactivation of cysts in drinking water 7. interaction of the parasite with intestinal lining (pathology, inflammation, e.a..)

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Adriaensen Dirk
• Co-promoter: Cos Paul
• Fellow: Bénéré Ely

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

For most infectious diseases, chemotherapeutics are still required for disease control as vaccines are generally lacking. In addition, drug resistance has become a critical issue, which endorses the need for continuous drug research. LMPH is actively involved in the identification of new synthetic and natural lead compounds, with a particular focus on the tropical protozoal diseases Leishmaniasis, sleeping sickness, Chagas disease and malaria. Validated in vitro and in vivo test systems and drug screening technologies have been developed. The Drugs for Neglected Diseases Initiative (DNDi) has access to compound libraries which have never been tested for the listed diseases. In this project, both groups have joined expertise and know-how to achieve a more productive drug discovery platform.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul
• Co-promoter: Delputte Peter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A biofilm is defined as a microbially-derived sessile or adherent community embedded in a matrix and irreversibly attached to a surface. Since biofilms exhibit a high resistance against biocides, this project will develop a method to detect Staphylococcus aureus biofilms. In addition, several known and new biocides will be evaluated for their capacity to inhibit biofilm growth or to destroy existing biofilms.

Researcher(s)

• Promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Treatment of the tropical disease leishmanisis is beconing more difficult be cause of the emergence of widespread resistance against the first-line drugs. Epidemiological studies on the prevalence and spread of drug-resistance forms a basis for the correct positioning of treatment strategies. This project will run a phenotyping of Leishmania donovani field strains and will develop molecular tools for the detection of natural SBV-resistance. More in particular, the following objectives are considered: 1. Identification of resistance markers that correlate best in natural SbV resistant field strains 2. Experimental verification of the role of the selected markers on the in vitro resistant phenotype 3. Evaluation of the developed molecular tools for SbV resistance in clinical samples of VL patients 4. Evaluation of the correlation between the presence fo R-markers and therapeutic failure after SbV treatment.

Researcher(s)

• Promoter: Maes Louis

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The search for a HIV vaccine, able to induce broad cross-neutralizing antibodies (BCNA) remains a top priority. BCNA can be found in a minority of chronically HIV-infected subjects. Based on their plasma, we will select the responsible epitopes, based o, a "peptide phage display" method. On the other hand, we have at our disposal several "antibody phage libraries", based on the bone marrow of patients with BCNA. Therefore, it will be possible to isolate new BCNA via the previously selected peptides. Possible applications include the development of a multi-component vaccine and therapeutic antibodies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Dieltjens Tessa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to better understand the mechanisms of HIV transmission in the female genital tract by the development of an "in vitro dual chamber model". In the apical chamber, various epithelial cell lines, representative of the different compartments of the female genital tract, are grown to confluence on a semi-permeable membrane. In the basal chamber primary target cells, including macrophages, dendritic cells and T cells, are present. In this system, we can check which are the determinants of transmission of both cell-free and cell-associated HIV and we can also investigate how to block transmission of course. The latter is important in the development of new preventive stategies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Gali Youssef

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

An environmental study of BU will be performed in endemic regions in Benin and DRC in collaboration with Beninese (PNLUB, LRM, UAC) and Congolese partners (PNLUB, UNIKIN, INRB, IPN, IME-hospital). A better understanding of the reservoir of M. ulcerans and the determination of environmental risk factors wil! be a great contribution to the control of the disease and will be able to develop adapted and affordable prevention tools.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Suykerbuyk Patrick

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Following primary infection a vigorous HIV-specific CD8+ T-cell immune response is initiated. Nevertheless HIV can escape an efficient immune response resulting in the development of a chronic disease, which causes depletion of CD4+ and CD8+ T-cells. The recent highly active anti-retroviral therapy (HAART) is unable to eliminate the virus. Therefore, it is important to develop novel therapies, which are based on the induction of an effective immune response that is able to eliminate infected cells or control the virus lifelong. In this project we want to develop this strategy in vitro. The two crucial elements are: - Using a broad range of possible virus sequences of the latent reservoir as antigen, to protect again virus escape. To express the whole latent reservoir, a PCR based technology will be developed to amplify provirus Gag DNA from infected autologous T-cells. - An optimalisation of the antigen presentation by dendritic cells, by modifying the dendritic cells with costimulatory molecules, to improve the CD4 and CD8 T-cell dysfunction.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Van Gulck Ellen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project has two equivalent main objectives: (1) To investigate the pathogenesis of clinical complications of Human T Lymphotropic Virus-l (HTL V-I ) in Peru. (2) To strengthen the academic capacity of the Institute of Tropical Medicine Alexander Von Humboldt in Lima. The strength of the research part relies on two elements: (a) the accessibility of a large patient cohort in Lima, with three types of complications (inflammatory, neoplastic and opportunistic infections) and the availability of asymptomatic HTLV-l-infected as well as -uninfected family members; (b) the integrated multidisciplinary approach to clinical, virological, immunological and genetic research questions. Using this research project as a "leverage", the diagnostic and clinical capacities of ITMA vH will grow and several young Peruvian technicians, clinicians, PhD students and one postdoc will be trained with the ultimate goal to constitute an intermediary academic staff who will be able to conceive and execute basic and clinical research in endemic infectious diseases. Basic knowledge on HTLY-l, as well as the guidelines resulting from this project will be extended to the Peruvian medical community and the health authorities.

Researcher(s)

• Promoter: Vanham Guido

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

PX-6518 is a triterpene saponin with a broad-spectrum antileishmania action. Its mode-of-action is still unknown and in vitro and in vivo research is planned to investigate 1/ compound-induced structural changes (histology, EM) of the different parasite stages, 2/ relation between selective accumulation into the phagolysosome and antileishmania activity and 3/ pharmacodynamics and toxicity in the visceral Leishmania hamster model (histopathology, serum biochemistry).

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Ludwig Annick

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The present PhD projects fits into the EMPRO project, which aims to develop new candidate microbicides (preventive anti-HIV drugs). The specific EMPRO objectives are (1) To design new compounds that target several steps in the viral cycle before integration; (2) To compare their activity and toxicity in a number of in vitro and in vivo models; (3) To test a few selected compounds in human phase I trials. Our task in this project is to test products in a model system that mimics the most important target cells during sexual transmission: dendritic cells and autologous CD4 T cells. We already identified some active and non-toxic compounds in the various classes. The first scientific question for this PhD project is whether combinations of good compounds from different classes show synergistic action in our model system, without inducing excess toxicity. The ultimate purpose is that microbicides will be very widely available. One unwanted consequence could be the transmission of resistant viruses, since seropositive women, not aware of their status, might also use the products. Therefore, a second focus of our project will be to compare the candidate microbicide in our in vitro model for their potency in HIV resistance induction. Clearly, amongst equally active and non-toxic candidates, we will select those that do not easily induce resistance.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Terrazas Aranda Katty

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

One of the main challenges ahead for the design of an effective HIV vaccine is the definition of true correlates of immune protection against HIV infection. Although it is still controversial which immune responses, humoral or cellular are most important in protection against infection, both types have been shown to contribute. Currently used ex vivo assays to measure anti-HIV cellular immune responses assess the immune response against a small part of the HIV virus, whereas for initial screening it would be more appropriate to increase the sensitivity of the assay as much as possible. Overlapping peptides are widely used but require a lot of cells and would be better used at a second or subsequent line. The use of infectious virus requires a level 3 security lab whereas inactivated virus would not be able to adequately monitor CD8+ T cell responses due to the lack of endogenous antigen presentation. Previous studies have succeeded to circumvent this difficulty by using single-cycle HIV-1 as stimulating antigens to stimulate HIV-specific CD4+ and CD8+ T cell responses. HIV pseudoviruses particles have been designed and are currently used to monitor in vitro virus neutralisation and the efficacy of potential anti-HIV drugs. This project aims to construct subtype-specific HIV-1 pseudoviruses as a source of HIV antigens as a first line screening assay to broadly monitor HIV-specific cellular immune responses in vitro. In order to stimulate HIV-specific cellular immune responses against a maximum of HIV-1 epitopes via MHC class I and II pathway, we want to construct HIV-1 pseudoviruses that contain all HIV-1 proteins as well as a pseudoviral genome that encodes for all HIV-1 proteins. The three main objectives of this project are: 1.Development of a technology to construct subtype-specific HIV-1 pseudoviruses, which can be used to present all HIV-1 antigens though natural antigen processing. 2.To compare the cellular immune responses measured with HIV-1 pseudoviruses with those responses measured with overlapping HIV-1 peptides, recombinant proteins and recombinant vaccinia viruses. 3.To assess correlations between cellular immune responses measured with HIV-1 pseudoviruses correlate with disease progression or protection against infection with HIV.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Beels Dominique

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The University of Antwerp (UA) and the Institute of Tropical Medicine Antwerp (IMTA) together with the pharmaceutical industry partner Tibotec have agreed to collaborate in lead-finding and lead-exploration for tropical & neglected diseases, such as malaria, leishmaniasis, sleeping sickness and Chagas disease. Practically, a test battery for medium throughput in vitro drug evaluation will be set up on the basis of the joint technical know-how to accommodate, among others, for the current screening needs by WHO-TDR. Compound (chemicals and natural products) acquisition through existing networks will continue and dedicated compound-handling logistics will be implemented. As a secondary objective, capacity will be created to assess `drug developability' through early pharmacological and pre-clinical profiling of selected `hits'. This project focuses on tropical diseases that remain of prime interest to WHO-TDR and offers realistic possibilities of identifying new leads.

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Cos Paul

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

M. ulcerans causes Buruli ulcer, which is a devastating and necrotic skin and subcutaneous infection that occurs in tropical countries especially in western and central Africa. Closely related to M. ulcerans is M. marinum. M. marinum is a waterborne mycobacterium that leads to demaciation and lethargy in fishes ending by dead. M. fortuitum, M. chelonae or M. abscessus cause similar ulcerations in fish and abscesses in humans. An infection in humans with M. fortuitum, M. chelonae or M. abscessus occurs especially after injections or vaccinations with non-sterile solutions. Although it almost never causes dead, it can bring serious complications along. The 5 species can be identified with current methods but subtyping upto subspecies or genotypic level is not available. Genotyping is important for the identification of possible virulent or non-virulent strains and it can lead to the precise recognition of reservoir and mechanism of infection. Typing on subspecies level can be necessary to determine an ideal antibiotics therapy. To isolate mycobacteria from water we will develop a rapid filtering method that enables us to concentrate the strong diluted concentration of mycobacteria. We will test different filter systems and elution media that are on top selective for mycobacteria.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Stragier Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

In collaboration with the Laboratory of Virology of the Centre Hospitalier Universitaire (CHU) Le Dantec in Dakar, Senegal a population of HIV-discordant couples will be followed up longitudinally. The role and function of HIV-specific T cells in protection against HIV infection will be studied in HIV-seronegative partners of HIV-positive patients with documented unprotected sexual exposure to HIV.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Tavernier An

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

An environmental study of BU will be performed in endemic regions in Benin and DRC in collaboration with Beninese (PNLUB, LRM, UAC) and Congolese partners (PNLUB, UNIKIN, INRB, IPN, IME-hospital). A better understanding of the reservoir of M. ulcerans and the determination of environmental risk factors will be a great contribution to the control of the disease and will be able to develop adapted and affordable prevention tools.

Researcher(s)

• Promoter: Kestens Luc
• Fellow: Suykerbuyk Patrick

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Following primary infection a vigorous HIV-specific CD8+ T-cell immune response is initiated. Nevertheless HIV can escape an efficient immune response resulting in the development of a chronic disease, which causes depletion of CD4+ and CD8+ T-cells. The recent highly active anti-retroviral therapy (HAART) is unable to eliminate the virus. Therefore, it is important to develop novel therapies, which are based on the induction of an effective immune response that is able to eliminate infected cells or control the virus lifelong. In this project we want to develop this strategy in vitro. The two crucial elements are: - Using a broad range of possible virus sequences of the latent reservoir as antigen, to protect again virus escape. To express the whole latent reservoir, a PCR based technology will be developed to amplify provirus Gag DNA from infected autologous T-cells. - An optimalisation of the antigen presentation by dendritic cells, by modifying the dendritic cells with costimulatory molecules, to improve the CD4 and CD8 T-cell dysfunction.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Van Gulck Ellen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

There still remains indistinctness about the nature of immune responses that are potentially protective against HIV infection and/or disease progression towards AIDS. According to the most recent data neutralizing antibodies as well as cytotoxic T-lymphocytes (CTL), supported by a strong CD4+ T-helper response, are essential for protection. The past years clear evidence was found of mucosal but also systemic cellular and humoral HIV-specific immune responses in persons who are frequently exposed to HIV but do not get infected. In 'HIV-exposed seronegative' (ESN) 'female sex workers' (FSW) in Gambia, Nairobi and Cote d'Ivoire HIV-specific T-helper as well as cytotoxic T-cell responses were found. Frequently used techniques to measure cellular immune responses in HIV+ patients are 'enzyme-linked immunosorbent spot' (ELISPOT) assay and the intracellular cytokine detection by flow cytometry. This latter method is mostly not sensitive enough to measure HIV-specific responses. The ELISPOT assay, on the contrary, has a higher sensitivity and is relatively simple and affordable. Unfortunately the classical ELISPOT assay does not allow the simple discrimination between HIV-specific responses derived from CD4+ or CD8+ T-lymphocytes. Mostly this is resolved by preceding cell subset depletions. Yet these can involve some important disadvantages, such as alterations in cell subsets and loss of antigen presenting cells. Our work hypothesis states that the characterization of HIV-specific CD4+ and CD8+ T-cell epitopes (by using a refined ELISPOT assay) in persons who are frequently exposed to HIV but did not get infected, is essential for the identification of protective immune responses against HIV.

Researcher(s)

• Promoter: Kestens Luc

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project