Enhancing vaccine trials across Europe and beyond

How did you first get involved in the vaccine field and how have your interests evolved?

PVD: My interest in preventing infectious diseases started when, as a young general practitioner in Antwerp, I began to encounter patients with HIV/AIDS. At that time, medical and therapeutic options were very limited and unfortunately I witnessed the deaths of many young homosexual men. I became interested in population health and embarked on a PhD in the prevention and transmission of hepatitis B within residents in mental institutions.

At that time, GSK had developed the first hepatitis B recombinant DNA vaccine and approached me to set up a study involving the institutionalized population. Around the same time, GSK also approached my colleague Peter Piot to conduct a similar study with a cohort of men who have sex with men in Antwerp. These two pivotal studies demonstrated that the first recombinant DNA hepatitis B vaccine was safe, immunogenic, and protective. This experience further deepened my interest in vaccines, infectious disease prevention, and public health.

Following my PhD studies, I established the Center for Evaluation of Vaccination at the University of Antwerp. Together with a team of nurses, doctors, project managers, and coordinators, we began assessing a range of vaccines, including those targeting hepatitis A, HPV, and polio. I later became a Professor of Epidemiology of Infectious Diseases and Vaccinology, teaching the current and future generations of healthcare providers.

How much are healthcare providers typically taught about vaccines?

PVD: Unfortunately, vaccines and infectious disease prevention are treated as secondary in the academic curriculum at many European universities’ medical schools. This approach mirrors spending on infectious disease prevention in national healthcare budgets, often receiving less than 3% of the total budget. The more funding is invested in disease prevention, the higher the return on investment will be in 10–20 years, but our politicians, hospital doctors, and deans of faculties need to pay more attention to infectious disease prevention and vaccinology in medical education, and to prevention in general. For example, we recently published the results of a survey we conducted across several countries involving various professional and student groups, termed the Vaccine Training Barometer [1]De Waele A, Hendrickx G, Valckx S, et al. The Vaccine Training Barometer: assessing healthcare providers’ confidence to answer vaccine-related questions and their training needs. Vaccine 2024; 42(9), 2421–2428. . We found that pharmacists, general practitioners, other healthcare providers, and students reported receiving little to no training in vaccinology. As a result, many healthcare providers feel unprepared to answer questions from patients or their caregivers, which can only exacerbate vaccine hesitancy in our society. This problem needs to be addressed because better education could make a huge difference: this should be reflected not only in medical educational programs but also in pharmacy, nursing, and midwifery curricula.

What projects are you excited about right now?

PVD: Continuing the vaccine education theme, we have been working on a new initiative with the WHO’s European Office and colleagues at University of Antwerp to design a game called ‘Immune Patrol’. This digital game for children aged 10–12 years includes components for both teachers and pupils. Modules cover topics in infectious diseases, such as how they spread, population or herd immunity, what vaccines are and how they work, and how to validate information. The game is now being used in several countries and has been translated into multiple languages. Currently, we are piloting ‘Immune Patrol’ in French, Dutch, and German-speaking schools in Belgium. By the end of September, we expect to see the results of this trial, and our goal is to present these findings to the Minister of Education and propose implementing this program in all schools nationwide.

Secondly, a significant part of my work is dedicated to improving and accelerating the conduct of vaccine trials, both within our country and internationally. We are seeing a range of novel vaccines emerging from various pipelines, and it is crucial to understand what is in development and how to address these vaccines, so they can be registered rapidly. This is particularly important for preparing for future pandemics, especially if we can accelerate and simplify the whole process.

I believe the model for the future is to identify and bring together expertise, both within and outside the country, rather than duplicate each other’s efforts. This is one of the key lessons from the COVID-19 pandemic—in order to succeed, we must foster collaboration, which includes combining regional, national, and European/global expertise and nurturing extensive communication, trust, and transparency.

This approach has been put into practice in a project called MusiCC, which involves collaboration of Belgian teams with the UK, USA, Singapore, and the Netherlands. MusiCC is a CEPI/Health Emergency Preparedness and Response Authority consortium focused on mucosal immunity in human coronavirus infections. The goal of this project is to support the development of the next-generation nasal or inhalation COVID-19 vaccines, specifically by examining how vaccines can block transmission via mucosal immunity.

We will use controlled human infection models (CHIMs), leveraging facilities in the UK, USA, Belgium, the Netherlands, and Singapore. The project will operate in parallel across these locations to increase the capacity and accelerate assessments. We will vaccinate a population with these vaccine candidates and also include a placebo group. Both groups will then be exposed to a challenge agent to determine if the vaccine not only provides protection against disease but also interferes with the transmission. This approach aims to control upper respiratory tract infections on a larger scale, which will hopefully have a major impact on future pandemics. For example, the next generation of vaccine candidates for flu and RSV will hopefully focus not just on individual protection but also on preventing transmission in communities.

Finally, we have our clinical trial facility, Vaccinopolis, supported by both the Belgian and Flemish governments. This relatively new campus facility allows us to conduct vaccine trials from Phase 1 through Phase 4, as well as CHIM studies. During the pandemic, we also received support to collaborate with the Université Libre de Bruxelles and Arnaud Marchant to establish the virtual European Plotkin Institute for Vaccinology that connects two research teams from different universities. While we handle the conduct of trials, the other research team focuses on immunoassays and other experimental immunological studies in their laboratory.

The VACCELERATE Consortium held a workshop last year on adaptive platform trial methodology—how could this concept be implemented for vaccine clinical trials going forward?

PVD: During the VACCELERATE Consortium workshop [2]Bethe U, Pana ZD, Drosten C, et al. Innovative approaches for vaccine trials as a key component of pandemic preparedness—a white paper. Infection 2024; doi: 10.1007/s15010-024-02347-1. , we aimed to unite expertise in vaccine trial sites and vaccine assessment. Coordinating this during the COVID-19 pandemic was challenging, but we learned many lessons from this project and discussed several key challenges.

Firstly, vaccine trials are very different from therapeutic trials. Researchers who are accustomed to conducting therapeutic trials may assume they can easily transition to vaccine trials, but vaccine trials require specialized laboratories to analyze immunological readouts. This necessitates standardization, harmonization, and validation over different laboratories, which is challenging, but so needed.

Secondly, the study participants of vaccine trials are mostly healthy volunteers, and would ideally be immunologically naïve, which is especially challenging for widespread conditions such as COVID-19.

Another key discussion point was how to accelerate the conduct of vaccine trials by utilizing adaptive design, common in therapeutic trials. Adaptive design allows for the activation or design of multiple arms within a protocol. These arms are approved in advance, enabling informed decisions about whether to continue certain arms, adjust sample sizes, add new trial arms, or include specific populations later in the vaccine trial. For example, the elderly and pregnant women are often excluded from vaccine trials. Utilizing adaptive design allows for adding new trial arms for these specific groups if initial Phase 1 and Phase 2 data on safety are promising.

On a similar vein, an important strategy for improving pandemic preparedness is to develop template protocols during inter-pandemic periods. These protocols could be pre-approved by the European agency and ethics committees. Since many aspects, such as vaccine composition or platforms, are likely to remain consistent, this approach could significantly accelerate the entire process. In addition, in the interpandemic period companies and research institutions should be able to explore research questions, such as vaccine combinations and co-administration, different schedules, and methods of administration, in greater detail than may be possible when facing an urgent pandemic threat.

How is the role of CHIM trials evolving?

PVD: So far, only a limited number of vaccines have been approved through CHIM studies, with the cholera vaccine being one example. However, we have seen advances in the utilization of CHIM, especially in the UK during the COVID-19 pandemic. While these trials did not necessarily lead to immediate clinical applications, they have greatly enhanced our understanding of infectious diseases and could accelerate the selection of prototype vaccines in the future.

Instead of recruiting tens of thousands of participants to a randomized controlled trial that might end up proving the vaccine ineffective, a much smaller CHIM-based trial could help to determine whether a vaccine candidate shows promise early on, saving time and money.

Another advantage of a CHIM study is its ability to provide better documentation for vaccines against various pathogens. Field trials for pan-coronavirus or pan-influenza vaccines are challenging because the circulating strains are often unpredictable. However, CHIM trials allow for exposing volunteers to specific challenge agents, such as H2N3, H5N1, and H1N1, and evaluate whether the vaccine offers protection against these variants.

CHIM trials can also be used to study transmission by mimicking a household setting within a contained environment. These controlled settings minimize the risks to the environment and volunteers, allowing researchers to assess whether a vaccine effectively blocks transmission. Ethics committees closely assess these practices, but the concept is to create an ‘artificial epidemic’ within a fully contained facility to document individual protection and transmission blocking potential. This approach will allow researchers to explore new endpoints related to mucosal immunity and test them to determine what correlates best with protection.

Overall, adaptive design trials and prototype vaccine documentation open numerous new opportunities. The next step is to ensure that the EMA and Ethics Committees is also aligned with this evolution of CHIM trials, so we will have many meetings and constant communication with the regulators to clarify the risks involved, how they are mitigated, and the data we aim to generate. It is important that these data can also be used in approval, registration, and license packages by companies or research institutions.

What challenges arise in the availability, source, and origin of pathogen strains for CHIM studies?

PVD: First and foremost, the number of currently available challenge agents/pathogen strains in the public domain is limited. Additionally, some challenge agents are restricted to private domains, making them more expensive. Therefore, it is crucial to set up a library of challenge agents, and we are currently working on this alongside colleagues. The goal is to create a publicly available library of challenge agents for researchers, ensuring that these agents are standardized in terms of dose, characteristics, preparation, and GMP. This standardization is essential for comparing results across different CHIM studies.

We are currently in an inter-pandemic period—an ideal time to build a bank of challenge agents and seek support from governments, organizations such as CEPI and Bill & Melinda Gates Foundation, and potentially private companies.

A further goal is to conduct modeling studies to determine the appropriate concentrations and dosages of challenge agents that trigger an infection, and sufficient attack rate without causing severe disease.

What challenges have been raised by the new European Clinical Trial Regulation and how can the EU retain a robust clinical trial ecosystem?

PVD: The new Clinical Trial Regulation aims to harmonize and centralize clinical trial procedures across EU countries. This is a rational and important goal, and this initiative is fantastic. However, in practice, it has led to a tripling in the time needed to get the approval to conduct a clinical trial. This means that many companies are now choosing not to do trials in EU countries and instead go in search of faster processes elsewhere. While Europe offers competitive quality and price, the speed of the process is just as important.

It is essential to maintain and enhance the European vaccines ecosystem, which encompasses manufacturing, small and medium-sized biotech companies, diagnostics, and academic partners. This unique ecosystem could lose some of these key players if we do not find a way to work more efficiently with the European Commission and streamline the approval mechanisms.

This could be improved by centralizing the information system between regulatory, ethics and research bodies. Sometimes questions can quickly be answered by the principal investigator or the research team, but the distance between decision-makers and those who are drafting the questions is much longer than it used to be in the past, when local relationships with investigators and familiarity with facilities helped expedite processes. Now, everything needs to be checked, which is important but time-consuming. Therefore, finding ways to shorten these communication lines is one of the priorities. Moreover, vaccine trials often have unique demands, such as recruiting a larger number of healthy volunteers and spanning multiple countries and sites, which adds more complexity.

What is the most important recent innovation in the vaccines development field, and why?

PVD: The most essential development, in my view, is on the one hand the growing role CHIM studies will play in the future in the assessment of prototype vaccines and monoclonal antibodies, and on the other hand the increasing focus on mucosal immunity, which was often under-examined and under-assessed due to other priorities. While it is amazing to witness the launch of successful pertussis and influenza vaccines, we could pay more attention to how the next-generation vaccines could block transmission. Some progress is already being made in the development of mucosal immunity-based vaccines, especially in the pertussis and hopefully COVID-19 field.

The focus on mucosal immunity opens up new possibilities for public health. By understanding and harnessing mucosal immunity instead of just humoral or cellular immunity, we can potentially develop vaccines that not only protect individuals but also reduce transmission rates, which would also offer broader community protection. Consequently, correlates of protection will probably have to be redefined, taking mucosal immunity biomarkers into account.

Finally, the evolution of new ways of administering vaccines, intradermally as well as mucosal, are important innovations in the vaccine field. We should not forget that it is not the vaccine that saves lives but the vaccination!

What’s next for your work?

PVD: The main focus for my whole team and I in the next 5–10 years will be, the conduct of Phase 1 and 2 adaptive design vaccinology trials and CHIM trials in the Vaccinopolis infrastructure at the University of Antwerp, to help accelerate the development of novel vaccines.

My second focus will be underlining the importance of vaccinology in (para)medical education.

And finally, transferring my duties, knowledge and expertise to my successor and team members, will be my third focus.

References

1. De Waele A, Hendrickx G, Valckx S, et al. The Vaccine Training Barometer: assessing healthcare providers’ confidence to answer vaccine-related questions and their training needs. Vaccine 2024; 42(9), 2421–2428.  Crossref

2. Bethe U, Pana ZD, Drosten C, et al. Innovative approaches for vaccine trials as a key component of pandemic preparedness—a white paper. Infection 2024; doi: 10.1007/s15010-024-02347-1.   Crossref

Biography

Pierre Van Damme obtained his PhD in Epidemiology and Public Health in 1994. He has been active for more than 35 years in vaccine trial and infectious disease research, and conducted more than 500 vaccine trials as PI or co-PI. Since 2000, he has been full Professor of Vaccinology at the University of Antwerp, Antwerp, Belgium and teaches vaccinology in national and international courses. Pierre Van Damme heads the Centre for the Evaluation of Vaccination (CEV, University of Antwerp), which he founded in 1994, and is director of Vaccinopolis, a unique facility in Europe for vaccine trials and human challenge studies. With Arnaud Marchant, he set up the recently founded European Plotkin Institute for Vaccinology, an initiative to accelerate the evaluation of vaccines for pandemic and endemic pathogens. The CEV is a WHO Collaborating Centre for the WHO European Region for the control and prevention of infectious diseases. Pierre Van Damme has been a regular advisor for national and international organizations for more than 25 years, including the Belgian National Immunization Technical Advisory Group, and the World Health Organization (European Regional Office and Headquarters). He has been appointed as chairman of the European Technical Advisory Group of Experts on communicable diseases and vaccines for the WHO European Region (ETAGE; 2005–2015). Pierre Van Damme has received several awards: the Research Award of the University of Antwerp, the Belgian Social Medicine Award ‘Jean Van Beneden’ for his work on the introduction of universal hepatitis B immunization programs; the prestigious Bill Marshall award of the ESPID society (2014); the ACRP (Association of Clinical Research Professionals) with the European Outstanding Leadership Award (2017); the prestigious Paul Harris Fellowship by the Rotary Foundation 2017); the Balmis Distinction Award (Almeria, Spain, 2017), the AHA Antwerp Innovation award (2019) and the science communication award UAntwerpen (2021). He has been a member of the Belgian Royal Academy of Medicine since 2008.

Affiliations

Pierre Van Damme MD PhD
Full Professor, Faculty of Medicine and Health Sciences,
University of Antwerp
Antwerp, Belgium
and
Director, Centre for the Evaluation of Vaccination (UAntwerp),
WHOCC,
Antwerp, Belgium
and
Director Vaccinopolis (UAntwerp),
University of Antwerp

Authorship & Conflict of Interest

Contributions: All named authors take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Acknowledgements: None.

Disclosure and potential conflicts of interest: The author is PI or co-PI of vaccine trials for which the university obtains grants.

Funding declaration: The author received no financial support for the research, authorship and/or publication of this article.

Article & Copyright Information

Copyright: Published by Vaccine Insights under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Attribution: Copyright © 2024 Van Damme P. Published by Vaccine Insights under Creative Commons License Deed CC BY NC ND 4.0.

Article source: Invited.

Interview conducted: Jul 31, 2024; Revised manuscript received: Sep 4, 2024; Publication date: Sep 12, 2024.