Alex Vorsters TT. asst. research professor

Research Alex Vorsters

Research team

Expertise

Prof. Vorsters is involved in several vaccine preventable disease projects including the Viral Hepatitis Prevention board (www.vhpb.org). Since 2015 he coordinates the activities of the Human Papilloma Virus Prevention and Control board (www.hpvboard.org). He got his Phd Medical Sciences in 2016 on detection of HPV DNA in urine and monitoring the impact of HPV vaccination. In 2020 he became Associated Professor and he is currently coordinating a research team that investigates the use of first void urine as a liquid biomarker source: in cervical cancers screening programs, for follow-up of HPV vaccination programs and other genital tract infections in women.

Exploring the ideal genital tract liquid biopsy: standardization of anti-HPV antibody detection in first-void urine for non-invasive vaccine monitoring. 01/11/2023 - 31/10/2025

Abstract

To date, invasive clinician-collected cervical samples, blood, and vaginal samples are still the primary methods to monitor disease and immune responses to vaccine-preventable genital tract infections. Replacing these samples with a specimen that is non-invasive and can be self-collected at home, such as the initial or first-void urine (FVU) stream, could have major acceptance and feasibility advantages and could drastically facilitate the logistics of clinical trials and future epidemiological studies. Initial results of experiments using FVU samples for immune response monitoring are promising. Nevertheless, overall standardization is essential for FVU to become the ideal genital tract liquid biopsy in vaccine research. With my PhD project, I wish to contribute to this aspect by using Human Papillomavirus (HPV) infection and vaccination as a model. Thereby, I will mainly focus on the immunogenicity of HPV vaccines and the monitoring of immune responses using FVU as a non-invasive liquid biopsy. As this will allow identification of anti-HPV antibodies as a normalized and standardized prediction tool for the immunization status of women, I believe this project will ultimately improve follow-up in HPV vaccination studies and programs. If my project proves successful, and FVU can replace other sample types, applications will largely extend the sexually transmitted infection (STI) field, contributing to the advancement of both personal and public health.

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  • Research Project

Vaccinating Europe to protect against the cancers caused by HPV (PROTECT-EUROPE). 01/01/2023 - 31/12/2024

Abstract

Gender-neutral HPV vaccination is a flagship policy in Europe's Beating Cancer Plan. If implemented throughout the EU with high levels of uptake, it has the potential to eliminate all the cervical, anal, vaginal, penile, head and neck cancers caused by HPV, around 67,500 new cases a year in the Member States. A key challenge to achieving high vaccine uptake is overcoming vaccine hesitancy, often based on concerns about safety. In most countries, uptake is currently too low to achieve 'herd protection'. The PROTECT-EUROPE project aims to tackle this problem on two levels. First, it will provide information and training on optimising one-to-one communication with young people and their parents/carers for the wide range of healthcare professionals involved in HPV vaccination. The training programmes will be delivered online and will be cascaded into Member States via a training-the-trainers approach. Secondly, the project will provide Member States and civil society organisations with a role in public health with guidance and a set of campaign tools aimed at young people and their parents/carers that can be used to encourage vaccination. The campaign tools will be designed for use across a range of platforms, including social media, websites, posters and leaflets. The potential of sport, specifically soccer, as an influencer will be explored. Particular attention will be paid to addressing issues of equality and diversity. All the project's outputs will be made available via an accessible online hub and disseminated via a final project report and a high-level event. The whole project will be independently evaluated by an academic institution. 34 organisations from 17 countries and a wide range of backgrounds (including oncology, general practice, pharmacy, nursing, patients, young people, public health, soccer), plus a wide range of experts, are members of the PROTECT EUROPE consortium. Nine of the countries represented have a GNI inferior to 90% of the EU average.

Researcher(s)

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Project type(s)

  • Research Project

Reaching more women in cervical cancer screening with a better prediction of their cancer risk. 01/01/2023 - 31/12/2024

Abstract

Cervical cancer is a major impact on public health, causing approximately 150 deaths in Belgium each year. Despite that there is a screening program in Flanders, 37% of the population eligible for cervical cancer screening is not reached by the current program that is based on analysing cervical smears (pap smears). Here, self-sampling, potentially done at home, could pose an alternative strategy for this hard-to-reach population. Infection with the human papillomavirus (HPV) is the cause of nearly all cervical cancer cases. Consequently, HPV detection is currently implemented as screening test. In case HPV is detected, an additional test (triage) is necessary to avoid overtreatment as the majority of HPV infections are spontaneously cleared and do not result in cervical cancer. For this triage the presence of aberrant cells in the pap smear is assessed. HPV detection performs well on self-samples, however, triage by detecting aberrant cells is not possible in this sample type. We will develop a test in which the detection of HPV and triage can be performed in one step on self-samples (as well as traditional cervical samples). As such we hope to reach more women and disturb less. Indeed, fewer women will need to be referred for follow-up causing less (emotional) distress. Thus, in this project we aim to reach more women in cervical cancer screening and give them a better prediction of their cancer risk.

Researcher(s)

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  • Research Project

Developing a combined screening and molecular triage approach for cervical cancer based on HPV detection, quantification, genotyping and DNA methylation in self-samples. 01/11/2022 - 31/10/2024

Abstract

37% of the population eligible for cervical cancer screening in Flanders is not reached by the current program. Here, self-sampling could pose an alternative strategy for this hard-to-reach population. Persistent infection with the human papillomavirus (HPV) is the cause of nearly all cervical cancer cases. Consequently, HPV DNA detection is considered the superior screening test to date due to its increased sensitivity as compared to cytology. However, it is associated with a lower clinical specificity as the majority of HPV infections are spontaneously cleared and do not result in clinically relevant disease. Thereby an additional triage step is necessary to prevent over-referral and potentially overtreatment which can be done by cytology. HPV DNA-based screening can already be performed on self-samples, however, this is not the case for cytology. By developing a fully molecular, combined screen and triage approach (one-step) based on HPV DNA detection, quantification, genotyping, and DNA methylation and that can be applied on self-samples (as well as cervical samples), we will provide a solution for the current screen and triage challenges. This will avoid over referral and allow better guided management of women needing treatment, while simultaneously increasing the participation rate. As such, the morbidity and mortality of cervical cancer could be reduced and both the health of the patients as well as the costs for the healthcare system would be positively affected.

Researcher(s)

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  • Research Project

Vaccine and disease monitoring 01/10/2022 - 30/09/2027

Abstract

The ability to easily obtain appropriate and reliable biological samples is critical to advance life sciences and public/personal health. Having a sample that is non-invasive and can be self-collected at home has major acceptance and feasibility advantages. Our team demonstrated that first-void urine (FVU) samples can replace clinician collected cervical samples to prevent cervical cancer caused by the Human Papilloma virus (HPV). Using the initial or first void urine stream is crucial here. Indeed, the outer layers of the epithelium of the genital tract exfoliate and together with the genital mucus form the utero-cervico-vaginal-smear, it accumulates between the labia minora, around the urethral opening and upon initiation of urination this discharge is washed away with the FVU. URISAMP uses HPV infection and vaccination models to prove the hypothesis that FVU is the ideal liquid genital tract biopsy to monitor immune response for women. URISAMP will 1) identify and validate analytical methods to detect the relatively low and fluctuating concentration of potential biomarkers in FVU; 2) provide protocols to study neutralizing antibodies and look at antigen-antibody interaction; 3) demonstrate how FVU sampling can enhance our knowledge regarding the biology of HPV, genital tract immunology, mechanisms of infection and transmission, the biological basis of prevention and potential correlates of protection. URISAMP will contribute to simplify and facilitate sexually transmitted infection (STI) vaccine research and provide valuable data for disease modelling. Moreover, if URISAMP proves successful, and FVU can also replace other samples types (e.g.blood), applications will largely extend the STI field, and its impact as a novel diagnostic and prognostic tool for health assessment will be substantial.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Increasing knowledge and understanding of Chlamydia trachomatis infection and future vaccine monitoring using noninvasive genital tract liquid biopsy sampling. 01/10/2022 - 30/09/2026

Abstract

Chlamydia (C.) trachomatis is a highly prevalent sexually transmitted bacterial disease, with 127 million infections reported in 2016. In women, genital tract infections by C. trachomatis can cause severe complications, including infertility, ectopic pregnancy, and chronic pelvic pain. In addition, the impact on susceptibility and transmission of other pathogens, such as HIV, has been reported. There is a consensus that prophylactic vaccination against C. trachomatis would be an important tool in our fight to control the worldwide impact of C. trachomatis. However, vaccine development, already being investigated for more than a century, is hampered by insufficient knowledge of the complex biology of C. trachomatis and its adaptations to evade interactions with the immune system. Current know-how emphasizes the importance of IFNɣ production and neutralizing antibody production as part of a successful immune response. Interestingly, the specific correlates of protection against infection are still to be revealed. This PhD will build on the know-how that is being established by our group using a first-void urine (FVU) sample for monitoring the impact of HPV vaccination programs. We have demonstrated already that FVU sampling can be effectively used to detect the presence of HPV infection and to monitor the humoral immune response. The developed tools to study the pathogen-immune system interaction will be adjusted for the follow-up of C. trachomatis infection and potential vaccine impact.

Researcher(s)

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Project type(s)

  • 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.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Disease and vaccine monitoring based on non-invasive genital tract liquid biopsy sampling (URISAMP). 01/05/2022 - 30/04/2027

Abstract

Disease and vaccine monitoring based on non-invasive genital tract liquid biopsy sampling. The ability to easily obtain appropriate and reliable biological samples is critical to advance life sciences and public/personal health. Having a sample that is non-invasive and can be self-collected at home has major acceptance and feasibility advantages. Our team demonstrated that first-void urine (FVU) samples can replace clinician collected cervical samples to prevent cervical cancer caused by the Human Papilloma virus (HPV). Using the initial or first void urine stream is crucial here. Indeed, the outer layers of the epithelium of the genital tract exfoliate and together with the genital mucus form the utero-cervico-vaginal-smear, it accumulates between the labia minora, around the urethral opening and upon initiation of urination this discharge is washed away with the FVU. URISAMP uses HPV infection and vaccination models to prove the hypothesis that FVU is the ideal liquid genital tract biopsy to monitor immune response for women. URISAMP will 1) identify and validate analytical methods to detect the relatively low and fluctuating concentration of potential biomarkers in FVU; 2) provide protocols to study neutralizing antibodies and look at antigen-antibody interaction; 3) demonstrate how FVU sampling can enhance our knowledge regarding the biology of HPV, genital tract immunology, mechanisms of infection and transmission, the biological basis of prevention and potential correlates of protection. URISAMP will contribute to simplify and facilitate sexually transmitted infection (STI) vaccine research and provide valuable data for disease modelling. Moreover, if URISAMP proves successful, and FVU can also replace other samples types (e.g.blood), applications will largely extend the STI field, and its impact as a novel diagnostic and prognostic tool for health assessment will be substantial.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Cervical cancer screening based on first-void urine self-sampling to reach screening non-responders: ScreenUrSelf trial. 01/10/2021 - 30/09/2025

Abstract

The goal of the ScreenUrSelf trial is to increase cervical cancer screening attendance and compliance to follow-up by offering a first-void urine self-sampling alternative to women who are currently not participating in the organized screening program (non-responders). Offering a cost-effective, fully molecular (primary high-risk Human Papillomavirus (hrHPV) testing, and if positive methylation marker triage) first-void urine self-test with high preference and compliance to follow-up has the potential to increase screening coverage among non-responders whilst reducing cervical cancer related morbidity and mortality. If embedded in the organized cervical cancer screening program, this could positively impact both the patient's health as well as reduce costs for the Flemish healthcare system. Thus, the primary scientific goal of this project is to evaluate the (cost-)effectiveness of four different self-sampling strategies (first-void urine vs vaginal self-sampling, via an opt-in or opt-out strategy) to women who do not participate in the Flemish organized cervical screening program, compared to the standard recall letter and no intervention. Secondly, a novel follow-up "reflex" test will be evaluated in self-samples that tested positive for hrHPV.

Researcher(s)

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Project type(s)

  • 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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Project type(s)

  • Research Project

VAXINFECTIO-PD _ VAXINFECTIO: Vaccine & Infectious Disease Institute _ PD: Product Development. 01/01/2021 - 31/12/2026

Abstract

VAXINFECTIO-PD is an established Industrial Research Fund (IOF) consortium, well equipped to build an ecosystem offering research, valorisation, innovation and development to answer existing and new challenges in the field of infectious diseases and vaccinology. These domains fall within one of the valorisation domains of the Antwerp University, and the newly established business unit Antwerp Valorisation & Development (AVD) of the UAntwerp. The VAXINFECTIO-PD consortium built up a unique and extensive track record through research, services, spin-off creation and innovative pathways, in generating product concepts/prototypes and research platforms that form the basis of medical innovation. The various core research units have had an important international image in the recent years with publications in leading journals, coordination of several European projects, as well as active presence and involvement in international scientific and policy forums. For the 6-year period the IOF-consortium will further focus on 5 interlinked valorisation avenues, all creating or guaranteeing growth on the parameters P3, P4, P5 and P6: translational vaccination platform for improved and new preventive and therapeutic vaccines, prognostic and diagnostic platforms, core facilities (for cellular vaccines, human challenge studies and biobanks), infectious disease and immune modelling and prediction, and improved vaccine delivery and medical devices through product development.

Researcher(s)

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Project type(s)

  • Research Project

Coalition to strengthen the HPV Immunization Community (CHIC). 01/11/2020 - 31/10/2025

Abstract

This initiative serves to unite the efforts and resources of 4 partnering organizations, combining the efforts and expertise of colleagues from the International Vaccine Access Center at Johns Hopkins University (IVAC), Jhpiego, the Centre for the Evaluation of Vaccination at the University of Antwerp, and the Vaccine Confidence Project (VCP) at the London School of Hygiene and Tropical Medicine (LSHTM). Together, we are working to build and support optimized local programs, guide rapid country adoption of revisions in schedule recommendations, and accelerate HPV vaccine introduction. The overarching goal is efficient translation of implementation research findings to guide practice and more equitable access to immunization ideally within the context of a stable HPV vaccine market. The goal of this project is to accelerate progress in HPV vaccine introduction, access, and program optimization in Gavi-eligible countries.

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Project type(s)

  • Research Project

Monitoring HPV vaccine impact in low- and middle- income countries with repeat urine surveys. 01/10/2018 - 30/09/2025

Abstract

Monitoring the impact of HPV vaccination through surveys of HPV DNA prevalence in urine samples from adolescents. Many low/middle-income countries are implementing national human papillomavirus (HPV) vaccination. Establishing baseline pre-vaccination prevalence is crucial to quantify later the impact of a vaccination program. HPV prevalence can be estimated in school-attending women aged 18 to 20 years by urine-based surveys according to a standardized protocol for study population recruitment, urine collection, DNA extraction, and HPV testing and genotyping. In addition to HPV also Chlamydia can be tested on the same samples.

Researcher(s)

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Project type(s)

  • Research Project

Evaluate and compare the accuracy of tests potentially applicable on vaginal self-samples and urine samples, where cervical samples taken by a clinician provide the comparator material. 22/07/2022 - 30/10/2022

Abstract

Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting.

Researcher(s)

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Project type(s)

  • Research Project

Validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples (Valhudes study). 25/11/2019 - 31/12/2022

Abstract

Back ground: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations. Objectives: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples. Study design: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies. Results: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene). Conclusion: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self sample device combinations that can be translated to a primary screening setting

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

First-void urine: a potential source to monitor humoral immunity. 01/01/2019 - 31/12/2020

Abstract

Feasibility of first-void (FV) urine sampling to monitor the impact of Human Papillomavirus (HPV) vaccination has been demonstrated, mainly focusing on urine as sample to assess viral endpoints. However, equally important to confirm immunogenicity of the prophylactic HPV vaccines, in addition to the absence of persistent HPV DNA infections, is monitoring immune response against HPV. It is assumed that the presence of neutralizing anti-HPV antibodies that transudate or exudate at the anogenital sites are critical for vaccine induced protective immunity. As such, detection of anti-HPV antibodies will be an important addition to the existing viral endpoints. Interestingly, the presence of transudated HPV vaccine-induced anti-HPV antibodies, in cervicovaginal secretions (CVS) has already been confirmed by several groups, justifying our idea to look for these antibodies in FV urine. Based on the same theory behind identifying HPV DNA in FV urine, this sample may also harbor anti-HPV antibodies originating from mucus and exfoliated cells from the female genital organs, including the cervix. To the best of our knowledge, the presence of anti-HPV antibodies in (FV) urine has never been investigated. Being able to assess these in an easy and non-invasive manner will be a major advantage for epidemiological and large population studies and for follow-up of HPV vaccination trials and programs. As a result of this project, ample new applications in other fields will be created, benefiting from monitoring the humoral immune response non-invasively at large scale, reducing the need for blood-sampling.

Researcher(s)

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Project type(s)

  • Research Project