Research team

Expertise

- In vitro and in vivo pre-clinical models of (viral) infectious diseases. - pre-clinical evaluation of vaccines - Development of vaccines: inactivated, attenuated, DNA and RNA based, vector vaccines - Generation of recombinant viruses using BAC based virus plasmids - reverse vaccinology - virus detection in and isolation from patient samples - Analysis of immune responses to viral infections (serology, antibodies, cellular immunity) - Antibody and nanobody (single domain antibody) development, production and modification. - Ultracentrifugation - PCR-based detection and quentification of viruses

Wastewater-based epidemiology of infectious diseases: an essential tool for pandemic preparedness and surveillance of endemic diseases. 15/07/2024 - 14/07/2025

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.

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  • Research Project

Development of virus-specific anti-NS1 antibodies and expression system for flavivirus recombinant NS1 for use in neurotropic flavivirus diagnostic, therapeutics, and vaccination development (Flavivirus_NS1_project). 15/02/2024 - 15/11/2024

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.

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  • Research Project

Defining a Correlate of Protection (CoP) for Respiratory Syncytial Virus (RSV): focus on the F protein and infants. 01/11/2023 - 31/10/2025

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.

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  • Research Project

Development of virus-specific anti-NS1 antibodies for use in neurotropic flavivirus NS1 antigen capture-based diagnostics. 01/11/2023 - 31/10/2024

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.

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  • Research Project

REspiratory Virus Repository ANTwerp (ReViRAnt). 01/01/2023 - 31/12/2024

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.

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  • Research Project

Respiratory co-infection models for fundamental and translational biomedical research. 01/11/2022 - 31/10/2024

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.

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  • Research Project

Elucidating the role of the Respiratory Syncytial Virus (RSV) peptide p27 and N-glycans in this peptide in protein structure and protective antibody responses. 01/10/2022 - 30/09/2026

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.

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  • Research Project

Development of a first-void urine based highly sensitive competitive HPV immunoassay. 01/10/2021 - 30/09/2024

Abstract

Detection of transudated antibodies in female genital secretions, washed away with the first fraction of urine – i.e. first-void (FV) urine –, has been confirmed. In addition, vaccine-induced HPV antibodies have been detected in FV urine of women using different immunoassays. Although good correlations between paired FV urine and serum samples have been observed, urinary antibody titres are at least 1000-fold lower than serum antibody titres. To be able to distinguish between both vaccinated vs. not-vaccinated and seroconverted unvaccinated vs. non-seroconverted unvaccinated women using FV urine, antibody yield and assay sensitivity need to be increased. The first step in our process to upgrade the detection of HPV-specific antibodies in FV urine, will be the production of HPV pseudovirions (PsV) for the quadrivalent vaccine types (HPV6, 11, 16, 18) to be used in a highly sensitive immunoassay (WP1). These PsV will be used to create HPV conformational monoclonal antibodies (mAbs) in mice using the hybridoma technology (WP2.1). These mAbs will be made type-specific by desensitisation for all other included HPV PsV types before immunisation with the HPV PsV type of interest. To evaluate the quality of the produced mAbs, a DELFIA time-resolved fluorescence (TRF) assay will be developed using the created PsV. In addition, the neutralizing abilities of the generated mAbs will be assessed using our in-house pseudovirion based neutralisation assay (WP2.2). The produced PsV and mAbs will then be used in a multiplex competitive highly sensitive ELISA using the TRF technology (WP3). It is clear that monitoring neutralizing HPV antibodies non-invasively by using FV urine samples has major advantages since it (i) is an easy to collect non-invasive sample, (ii) can also provide information about the infection by applying parallel DNA testing and, (iii) is suitability for at-home sampling (currently boosted by the COVID-19 pandemic). If successful, the created assay provides a very useful and almost unique tool to monitor neutralizing HPV antibodies. With only limited adaptations, the developed assay will be compatible with serum samples as well. Since there are limited HPV immunoassays available overall, and currently only one other assay (cLIA) detects specifically neutralizing antibodies, this assay will be of great value. In addition, the validated pseudovirions and HPV type-specific neutralizing mAbs will generate substantial interest and wide applications in the field.

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  • Research Project

Virus infections of man and animal 01/01/2021 - 31/12/2025

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.

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  • Research Project

Immunological control of Varicella zoster virus (VZV)-infected iPSC-derived brain models by steady-state and immune-compromised astrocytes and microglia. 01/01/2021 - 31/12/2024

Abstract

Varicella zoster virus (VZV) is a member of the herpesvirus family and is a highly successful and ubiquitous human pathogen. Both in children and in adults, varicella-related complications may lead to hospitalisation. While in children direct neurological complications may occur following primary infection (varicella), in adults vasculitis and neurological complications are not uncommon following reactivation of latent VZV (herpes zoster). With a clear link between VZV and neuropathology, it is inevitable that the immune system of the central nervous system (CNS) will be challenged by VZV. However, to date little is known about how astrocytes and microglia behave upon encounter of VZV in the CNS. In this project, we will address this question using an established human in vitro model of axonal infection of human induced pluripotent stem cell (hiPSC)-derived CNS neurons with fluorescent reporter VZV stains. Using this model, we will first longitudinal monitor how hiPSC-derived astrocytes and microglia influence the processes of VZV infection, latency and reactivation. Next, using iPSC models derived from VZV patients with mutations in POLRIII, we will investigate whether immune compromised astrocytes and/or microglia can control neuronal VZV infection. Altogether, these studies will help us understanding innate immune control of VZV in the CNS, and will allow - beyond the scope of this project – to develop novel strategies to prevent VZV spreading in the CNS.

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  • Research Project

V-CALSA – Visual Computer-Aided Lung Sound Analysis. 01/10/2020 - 30/09/2024

Abstract

Lung auscultation, which is the process of listening to breath sounds, is one of the most commonly used examinations to evaluate respiratory health. Over the last decades computational methods have been developed for the analysis of recorded lung sounds. Computer Aided Lung Sound Analysis (CALSA) aims to overcome limitations associated with standard lung auscultation by removing the subjective component of the process and allowing quantification of lung sound characteristics. To date, no accepted standard for data acquisition and analysis has been set and none of the proposed approaches have been successfully implemented in clinical practice. During this project we will develop a simple but robust visual representation for CALSA, which can be easily interpreted by health care professionals. Several clinical studies described in this project aim to validate this analysis and to study the ability of CALSA to measure the severity of RSV-bronchiolitis and the effects of respiratory therapy. Digital auscultation has the potential to be a sensitive, objective and non-invasive tool by providing regional information associated with local changes in the airways.

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  • Research Project

Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors (RespiriTB). 01/05/2019 - 30/04/2025

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.

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  • Research Project

Master in Vaccinology LIVE 03/09/2018 - 02/09/2024

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.

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  • Education Project

Development of a plasma device for rapid disinfection of contaminated hospital materials: Hospital‐Use Plasma Unit (HUP‐Unit). 01/09/2022 - 31/08/2023

Abstract

The SARS‐CoV‐2 pandemic has exposed how unprepared our society was in preventing the propagation of highly infectious diseases, protecting the healthcare providers and patients, and efficiently organizing the logistics, while managing large numbers of patients. For the past two years, hospitals have battled to mitigate the spread of the virus in their facilities, a challenge that included the need to daily dispose of thousands of unused, individually‐packaged medical products that could not be disinfected with the traditional disinfection methods. On average, the Antwerp University Hospital (UZA) produced around 250,000 kg of medical waste per year. In 2021, the amounts of medical waste increased by more than 10% compared to the pre‐COVID period. Globally, the pandemic not only increased the cost for hospitals, but it also increased the generation of waste around the world by 400‐500%. Moreover, at the height of the pandemic, there was even a critical shortage of medical supplies. Therefore, this was not only an environmental and financial issue, but also a serious healthcare burden. In order to be better prepared for future pandemics, we have prepared a mission‐oriented innovation project, which responds to a specific request from the Intensive Care Unit (ICU) at UZA. In our IOF‐POC CREATE project here, we aim to develop a non‐thermal plasma (NTP)‐based disinfection device to rapidly eliminate viruses from unused, individually‐packaged medical products: the hospital‐use plasma unit (HUP‐unit). Our HUP‐device will utilize a completely innovative cylindrical geometry design feature with materials to be disinfected, to enhance NTP generation and contact with a large volume of material, and ensure complete, uniform treatment. Indeed, we have to design a completely novel NTP device concept, which we will categorize as a 'moving‐bed' dielectric barrier discharge (DBD). By using the individually‐packaged hospital products as part of the NTP generation mechanism, our 'moving‐bed' DBD HUP‐unit offers a scalable solution to provide rapid disinfection in the hospital. Based on our understanding of plasma dynamics and computational plasma simulations, we have developed this theoretical design, but the feasibility of creating a working prototype remains to be seen. Therefore, in this IOF‐POC CREATE project, we will produce and validate our prototype HUP‐unit in the lab. If successful, our HUP‐unit will allow us to: i) mitigate shortages in individually‐packaged medical products; ii) reduce the waste produced by healthcare facilities and associated waste management cost; iii) reduce the incidence of hospital‐acquired infections.

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  • Research Project

Infrastructure for Diverse Applications of Single Cell Sorting and Dispensing using Microfluidics. 01/06/2022 - 31/05/2024

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.

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  • Research Project

COVID-19 national surveillance in wastewater: the variants project protocol. 23/05/2022 - 31/12/2023

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.

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  • Research Project

Development and validation of a bona fide iPSC derived human neuronal infection model to evaluate antivirals targeted against neurotropic viral infections. 01/05/2022 - 30/04/2023

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.

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  • Research Project

Unraveling direct interactions between the airway microbiota and respiratory syncytial virus. 01/10/2021 - 31/12/2023

Abstract

Viruses infecting the respiratory tract encounter a diverse resident airway microbial community (the microbiota). While the majority of research on the host-virus-microbiota nexus focuses on virus and microbiota interplay with host immunity, the impact of airway microbiota on viruses through direct interactions is poorly understood. The goal of this project is to come to a new understanding of how direct microbiota-virus interactions in the airways influence viral pathogenesis using respiratory syncytial virus (RSV) as a model. Innovative targeted isolation of RSV-binding bacterial strains from the airways of infants with RSV disease will be performed, in parallel with an in-depth functional and species-level taxonomic airway microbiome analysis. Focusing on beneficial bacteria, the effects of direct bacterial interactions with RSV will be analyzed using a suite of novel and state-of-the-art in vitro assays tailored to investigating the host-microbiota-virus nexus. Localization and properties of key anti-RSV bacterial compounds will be investigated. The effects observed at microbiome level and in vitro will be aligned with in vivo read-outs in an infant mouse model of RSV infection, to conclude whether they translate into clinically relevant outcomes. Understanding the role of direct interactions between airway microbiota and viruses will add a potentially groundbreaking new dimension to the interplay within the host-virus-microbiota nexus in the respiratory niche.

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  • Research Project

Analysis of Cars-CoV-2 in wastewater 20/01/2021 - 31/05/2021

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.

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  • Research Project

COVID-19 National surveillance in wastewater. 09/12/2020 - 14/09/2022

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.

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  • Research Project

Labo protocol. 14/09/2020 - 09/12/2020

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.

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  • Research Project

Wastewater as early warning system for COVID-19 surveillance 13/07/2020 - 31/08/2021

Abstract

This project aims at optimising an analytical protocol for the detection of SARS-CoV-2 RNA in wastewater. This will then applied to wastewater samples collected across Belgium to investigate the early warning character of the methodology. Triangulation of the wastewater data with other datasets (e.g. hospital data, infections) will be performed to investigate the complementarity of the data.

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  • Research Project

Characterization of a contemporary Respiratory Syncytial Virus isolate for use in pre-clinical and clinical research (ReSVistrain). 01/06/2020 - 31/08/2021

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.

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  • Research Project

SARS-CoV-2 RNA quantification in wastewater as complementary epidemiological indicator to monitor the epidemic. 01/06/2020 - 31/05/2021

Abstract

This project aims to detect SARS-CoV-2 RNA in wastewater sampled throughout Belgium as a complementary epidemiological indicator for the rapid and constant follow-up of the current epidemic at high spatial and temporal resolutions. This translational data-driven epidemiological research will provide direct added value to support and evaluate policy initiatives and to detect novel outbreaks. This project fills current knowledge gaps in monitoring the epidemic by providing prevalence estimates in the general population without the need for individual testing. Furthermore, through triangulation of our data with data from diagnostic testing and clinical surveillance, this project will make a more comprehensive prediction and control of the COVID-19 epidemic possible. The idea to measure SARS-CoV-2 RNA in wastewater as a proxy for its infection in the general population is innovative and epidemiologically highly informative as community-wide data can be obtained at high temporal (daily) and spatial (city or town) resolutions. This proposed wastewater surveillance strategy can be regarded as a sensitive early-warning tool and can substantially improve models/predictions of the ongoing epidemic. Specialists in wastewater-based epidemiology and virology are brought together in this consortium to make this project feasible within the proposed timeframe.

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  • Research Project

A platform to functionally assess clinically relevant respiratory parameters in small animal models for infectious and non-infectious pulmonary research. 01/01/2020 - 31/12/2021

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.

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  • Research Project

Identification of host-virus interactions contributing to immunopathology and disease severity in respiratory syncytial virus infections in children. 01/11/2019 - 31/10/2023

Abstract

Respiratory Syncytial Virus (RSV) is worldwide the leading cause of serious airway infections. It's so common that most children will be infected by age 2. In adults and older children, RSV symptoms are mostly mild and typically mimic a common cold, but younger children can develop very severe disease. Preventive and therapeutic options are limited and currently it is not clear why some children develop severe disease while others do not. We therefore aim to investigate host- and virus-related factors that influence disease severity. To reach this objective, we will isolate RSV from children with respiratory disease, characterize the isolates and objectify differences between them. Next, we will investigate the effect of different virus isolates on the immunological response induced by a human respiratory epithelial cell line, since epithelial cells are the primary target cells and are implicated in the pathogenic reaction upon RSV infection. Lastly we want to evaluate whether the same clinical isolate induces a different immunological response in respiratory epithelial cells isolated from different patients. We will thus not only gain fundamental insights in the causes of RSV induced disease, but we will finally also correlate the virus- and host-related risk factors identified in the lab with clinical symptoms observed in patients. With this project we aim to identify patients prone to severe disease in an early stage, thus improving therapeutic options and disease outcome.

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  • Research Project

ReLACT: Intranasal probiotics against respiratory viral infections. 01/10/2019 - 31/12/2020

Abstract

Respiratory Syncytial Virus (RSV) is the leading cause of severe lower respiratory disease in young children worldwide. Nearly all children are exposed to RSV by the age of 2, approximately 40 % will develop a lower respiratory tract infection such as bronchiolitis and up to 10 % of these children require hospitalization. Severe inflammation is a typical hallmark of the hospitalized children. Despite the discovery of the virus in 1956, prevention and treatment options for RSV are limited. In this project, an innovative approach based on the intranasal application of specific probiotic strains is explored to prevent the severe lung inflammation that follows the acute infection. We will investigate whether delivery of intranasal probiotics prior to RSV infection can prevent the development of severe RSV disease by functioning as immunomodulatory agents that can reduce RSV-associated inflammation. Furthermore, we will test if delivery of an RSV vaccine together with intranasal probiotics enhances both safety and efficacy of this vaccine.

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  • Research Project

Elucidating the mechanism of action of small molecule replication inhibitors of RSV and hMPV. 01/09/2019 - 31/10/2023

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.

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  • Research Project

Identification of host-virus interactions contributing to immunopathology and disease severity in respiratory syncytial virus infections in children. 01/10/2018 - 30/09/2022

Abstract

Respiratory Syncytial Virus (RSV) is worldwide the leading cause of serious infections of the lower airways, and nearly all children are infected with RSV by the age of two. RSV is responsible for different clinical presentations, ranging from mild to very severe disease. Limited preventive and therapeutic options are available, and furthermore, it is not clear why some infected individuals develop severe disease while others do not. We therefore aim to investigate host- and virus-related factors that may influence disease severity. To reach this objective, we will divide our research project in four different goals. Firstly, we will isolate RSV from patients and investigate which of two commonly used virus collection methods is best to obtain viable RSV isolates. Secondly, we will investigate the effect of different virus isolates on human respiratory epithelial cells, since these are not only the primary target cells, but also implicated in the pathogenic immune response upon RSV infection. Thirdly, we want to evaluate whether respiratory epithelial cells from different patients, react differently upon infection with the same virus, which may explain differences in disease severity observed in patients. We will thus not only gain fundamental insights in the causes of RSV induced diseases, but we will finally also correlate risk factors identified in the laboratory with clinical symptoms in patients, supporting the translational character of this research project.

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  • Research Project

The Biomolecular Interaction Platform (BIP) at UAntwerp. 01/05/2018 - 30/04/2021

Abstract

Physical and functional interactions between biomolecules play pivotal roles in all aspects of human health and disease. Gaining a greater understanding of these biomolecular interactions will further expand our understanding of diseases such as cancer, metabolic diseases and neurodegeneration. At UAntwerp, 7 research groups have joined forces to obtain the absolutely necessary equipment to measure these interactions with a Biomolecular Interactions Platform (BIP). This will allow to detect interactions and precisely determine binding affinities between any kind of molecule, from ions and small molecules to high-molecular weight and multi-protein complexes. The BIP will also allow to identify collateral off- targets, crucial in the drug discovery field. Access to a BIP will strongly support ongoing research projects and bring research within the BIP-consortium to a higher level. Since biomolecular interactions are highly influenced by the methodology, it is recommended to measure the interaction by several, independent techniques and continue with the most appropriate one. For this reason, the consortium aims at installing a BIP, consisting of several complementary instruments that each measure biomolecular interactions based on different physical principles. They wish to expand the existing Isothermal Titration Calorimetry with two complementary state-of-the- art techniques: MicroScale Thermophoresis and Grating- Coupled waveguide Interferometry.

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Improved respiratory syncytial virus (rsv) vaccines based on glycan modification of the viral fusion (f) protein. 01/04/2018 - 30/03/2019

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.

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An interdisciplinary study on the role of the HLA genes and T-cell diversity as risk factors for herpes zoster. 01/01/2018 - 31/12/2021

Abstract

Chickenpox is a consequence of primary infection of varicella-zoster virus (VZV). Afterwards, VZV remains latent in neural ganglia until symptomatic reactivation called herpes zoster (HZ, shingles). In this project, we will first develop a novel computational framework that will allow us to estimate the probability that a pathogen-derived antigen is adequately recognised by the major histocompatibility complexes (MHC) encoded by HLA genes. Antigen bounding by MHC molecules is a necessary step prior to recognition (and further management) of infected cells. Next, we will obtain HLA data from 150 HZ patients and 150 matched controls. This will allow us to estimate whether and which HLA A/B/C genes are enriched or depleted in HZ patients. Our computational framework will allow us to estimate which VZV proteins are most likely of importance in controlling VZV. We will assess whether the HLA data is readily translated into the diversity of the T-cell receptor (TCR) against VZV, and against which of the most important VZV proteins. Finally, we will differentiate blood-derived inducible pluripotent stem cells (iPSC) into neuronal cells, infect these neuronal cells with VZV and study whether depletion of VZV-specific T-cells affects VZV proliferation, thereby confirming our earlier obtained HLA-TCR predictions.

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  • Research Project

Nanobody-assisted targeting of sialoadhesin-positive macrophages to improve the treatment of tuberculosis. 01/10/2017 - 30/09/2020

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.

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Pathogenic processes of viral infections of mammals. 01/01/2016 - 31/12/2020

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.

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Lactobacillus exopolysaccharides as antipathogenic and immunomodulatory adjuvantia 01/01/2016 - 31/12/2019

Abstract

In this project the potential antipathogenic and immunomodulatory activity of exopolysaccharides of model Lactobacillus strains is investigated by in vitro and in vivo models. Methods for extraction, characterization and formulation of the exopolysaccharides are also optimized.

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Characterisation of a novel Respiratory Syncytial Virus (RSV) immune evasion mechanism and evaluation of the impact for development of novel vaccines and prophylactic and/or therapeutic antibodies 01/10/2015 - 30/09/2019

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.

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Medicinal Chemistry-Drug Discovery (ADDN). 01/01/2015 - 31/12/2020

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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Study of the role of immune cells in RSV infections. 01/01/2015 - 31/12/2018

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.

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  • Research Project

The potential of Lactobacillus exopolysaccharides and glycoproteins as safe vaccine adjuvants. 01/01/2015 - 31/12/2015

Abstract

Ligands of the innate immune system form an important new class of adjuvants, but the desired immunostimulation is often linked with toxicity and serious side-effects. These ligands or 'microbe-associated molecular patterns' (MAMPs) can also be found on the surface of lactobacilli with a 'generally regarded as safe' status. Various studies have demonstrated the specific effects of certain lactobacilli and their surface molecules, but the potential of MAMPs such as exopolysaccharides and glycoproteins of lactobacilli still requires further investigation. Hereto, the project is divided in three parts. First, the molecular interactions between the glycoconjugates and receptors such as Toll-like receptors and C-type lectins will be mapped. Next the in vitro immune response of these molecules in immunological important cells will be investigated. Finally, the potential of selected molecules will be validated in a mouse model.

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Equipment for high-speed refrigerated, preparative ultracentrifugation, automated gradient formation and fraction collection and analysis. 19/05/2014 - 31/12/2018

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.

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Mechanism of infection of sialoadhesin (Sn)-positive macrophages with respiratory syncytial virus (RSV) and its implications for inflammation and immune pathology during bronchiolitis. 01/01/2014 - 31/12/2017

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.

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Study of the role of membrane receptor signalisation in immune cell infection and regulation. 01/01/2013 - 31/12/2016

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.

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A drug discovery with a particular focus on tropical protozoa (leishmaniasis, malaria, sleeping sickness and Chagas disease) and mycotic infections (yeasts, dermatophytes and fungi). 01/09/2011 - 31/12/2016

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.

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Integrated evaluation of test compounds against Leishmania and Trypanosoma parasite species. 01/09/2006 - 31/10/2015

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.

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  • Research Project