Scientific Program

Day 1

KEYNOTE SPEAKERS
  • A novel Lyme borreliosis vaccine protecting against all major borrelia infections

    Valneva Austria GmbH
    Austria
    Biography

    Andreas Meinke is an expert in Micro- & molecular biology and infectious disease, with more than 18 years of experience in vaccine R&D. He graduated in Biology, performed his PhD work at the University of British Columbia in Vancouver, Canada and lectured at the University Vienna as an Assistant Professor. At Valneva he was instrumental for the development of the AIP technology and for the development of several vaccine candidates towards clinical testing. During his career, he has authored and co-authored more than 70 publications and filed more than 20 patents in the field of antigen discovery and vaccine research.

    Abstract

    Lyme borreliosis (LB) or Lyme disease is the most common vector-borne disease in the northern hemisphere and at present there is no vaccine available to prevent infections. Recent analyses showed that the number of infections in the US and Europe are largely underreported, emphasizing the need for an effective vaccine. An OspA (Outer surface protein A) based vaccine (LYMErix™) was previously shown to be efficacious against disease caused by the most prevalent B. burgdorferi in the US. In Europe, the majority of LB cases are caused by four different Borrelia species expressing six different OspA serotypes. Since Outer surface protein A (OspA) is one of the dominant antigens expressed by the spirochetes when present in the tick vector we have developed a vaccine for global use, consisting only of the C-terminal part of OspA which is sufficient for protection. To target the Borrelia species expressing the six different OspA serotypes prevalent in US and Europe, we have designed a multivalent OspA-based vaccine (VLA15), including three proteins, each containing the C-terminal half of two OspA serotypes linked to form a single fusion protein. The OspA fusion proteins were at least 85% triacylated which ensured high immunogenicity and were highly purified for further preclinical testing. Active immunization with the adjuvanted Lyme borreliosis vaccine VLA15 protected mice from a challenge with spirochetes expressing either OspA serotype 1, 2, 4, 5 or 6, using infected ticks or in vitro grown bacteria as a challenge. Further immunological analyses (ELISA, surface binding and growth inhibition) indicated that the vaccine can provide protection against the majority of human pathogenic Borrelia species, including OspA serotype 3. This rational designed VLA15 vaccine was therefore prepared for evaluation in a first-in-man study which currently ongoing.

  • Targeted vaccination and intrinsic adjuvant function: Next generation checkpoint control

    OncoQR ML GmbH
    Austria
    Biography

    Dr. Geert C. Mudde received a Ph.D. in immunology from the University of Utrecht in 1985 and started his international professional career at the Swiss Institute for Asthma and Allergy Research in Davos in 1989. In 1992 he joined the pharmaceutical/biotech industry, where he held several senior management positions at the Novartis Research Institute in Vienna, Austria, the Parke Davis Research Institute in Fresnes, France, Ingenium Pharmaceuticals, Martinsried, Germany, and at igeneon AG, Vienna, Austria. Finally, in 2006, while joining Baxter BioScience in Vienna as interim manager, Dr. Mudde co-founded the biotech company f-star Biotechnology, where he served as “Chief Scientific Officer” from 2007 to 2009. In 2009, together with Christof Langer, he started to develop the S-TIR™ technology platform for human specific therapeutic vaccines which led to the foundation of S-TARget therapeutics GmbH in 2010. Since then he serves as CSO and managing director for S-TARget therapeutics as well as for the S-TIR™ technology spin-off companies OncoQR ML GmbH and TYG oncology Ltd., which were both founded in 2013

    Abstract

    Using the S-TIR™ technology platform for human specific therapeutic vaccines OncoQR ML has developed two prototype vaccines for treatment of pancreatic cancer (TYG100) and breast cancer (OQR200). Vaccines derived from this platform consist of 2 modules, the disease specific module, “immunogen” and the generic module, “warhead”, which directs the vaccines to CD32 on antigen presenting cells, especially pDCs and B cells. The immunogen in oncology is a tumor associate auto-antigen, against which under normal conditions no Clinically relevant immune responses can be induced. However, in combination with the warhead, thanks to intrinsic check point control, the immune system generates very strong and rapid antibody and T cell immune responses. The responses are reversible and boostable, thus allowing fine-tuning of the clinical responses on a patient to patient basis. S-TIR™ vaccines in contrast to the current checkpoint inhibitors do not induce autoimmune disease and are tumor specific while mobilizing both arms of the immune system against the tumor.

Novel Vaccines - Research and Development | Cancer Vaccines | Chikungunya vaccine | Vaccines Discovery, Development & Formulation | DNA vaccines
Chair
Speaker
  • Chang Qing Xia
    Chang Qing Xia
    Time: 11:25-11:50
    Speaker
    Chang Qing Xia
    University of Florida, USA
    USA
    Biography

    Chang Qing Xia received his MD and PhD degree in China, and have been working at US for almost two decades. He is currently an Assistant Professor in the Department of Pathology, Immunology and Laboratory Medicine at University of Florida. His research is focused on dendritic cells and development of antigen-specific immunotherapies for autoimmune diseases and malignant tumors.

    Abstract

    Cancer immunotherapy has achieved extraordinary clinical outcomes over the last several years, particularly,chimeric antigen receptor (CAR) T cell therapy and immune checkpoint blockade therapy. An additional promising approach is to develop effective tumor vaccines for cancer prevention and treatment. The most common vaccine approach is inoculation of soluble antigens combined with adjuvants. Although this vaccine approach is most commonly employed worldwide, it has several disadvantages such as,a relatively large dose of antigen is required, an adjuvant is usually required, and only antigen-specific T cells in the local draining lymph nodes can be activated even if multiple injection sites are chosen. In this report, we took advantage of the lymphoid tissue homing property of immune cells to develop high-efficient antigen-delivery system to stimulate all antigen-specific T cells in the body. We wisely employed “click” chemistry method to efficiently couple the antigens to mouse spleen cells, then intravenously injected those antigen-coupled spleen cells into recipient mice and potently induced antigen specific CD4 and CD8 T cell response with heightened IFN-g producing capability. When we tested tumor antigen-coupled spleen cells in triggering anti-tumor immunity in melanoma and hepatocyte cancer mouse models, we found that this approach induced very strong anti-tumor immunity in both prophylactic and therapeutic experimental settings, and the animal survival was significantly improved. Immunological investigation showed that this approach induced both enhanced humoral and cellular immunity against tumor. Recently, we found that antigen-coupled allogeneic spleen cell injection induced equivalent, if not stronger, antigen-specific immune responses in contrast to injection of antigen-coupled syngeneic spleen cells, which could lead to off-the-shelf cell products for tumor vaccine. Our novel and unique approach is utilizing the homing nature of immune cells to distribute tumor antigens throughout the entire immune system and subsequently elicit strong anti-cancer immunity. Additional advantages over other vaccine approaches are minimal number of antigens required (only the antigens coupled to the cell membrane) and no adjuvant needed. Therefore, our approach holds high potential for clinical translation just like blood transfusion but without concerning about red blood cell type.

  • Ida Cristina Gubert
    Ethical issues in the production, design and clinical trials of new vaccines for emerging diseases in low income countries
    Time: 11:50-12:15
    Speaker
    Ida Cristina Gubert
    Federal University of Parana, Brazil
    Brazil
    Biography

    Bachelor degree in Biological Sciences from Universidade Federal do Paraná (1975), masters Degree in Genetics from Universidade Federal do Paraná (1986) and PhD in Biochemical and Molecular Pharmacology from Universidade Federal de Minas Gerais (2005) and Post-Doc in Bioethics in Clinical Research ( Facultad Latino Americana de Ciências Sociales, FLACSO, Argentina). Has experience in Immunology, focusing on Applied Imunology, acting on the following subjects: Immunology and Public Health. Chair Ethics Commitee in Research at Universidade Federal do Paraná and member of Group of Studies in Bioethics ( NEB) , Curitiba, PR

    Abstract

    Statement of the Problem: Since first developed by Jenner and Pasteur vaccines have shown to be an important tool for the eradication (cow pox) and prevention of communicable diseases with high morbidity and mortality rates, and became one component of public health policies. However, good quality housing, appropriate disposal of sewage, nutrition, education and adequate sanitary conditions have also been an important determinant in health promotion. In this way, upper level societies have witnessed a significant reduction of diseases such as zoonosis, communicable diseases and vector born infections. Nevertheless, populations in low income countries still face poor sanitary and living conditions which contribute to the emergence of new diseases. Recently countries in Latin America witnessed the epidemics of a vector borne viral infection that resulted in microcephaly to the fetuses born from infected women. Purpose: The purpose of this text is to present a reflection on the life conditions of these populations, their vulnerability, the need for new vaccines, the public health policies to be implemented and the ethical issues to be considered in this reality. Methodology: An analysis on the ethical issues concerning the development of new vaccines and their trials in low income countries. Conclusion & Significance: It is undeniable all benefits that have been reached in health promotion through immunization protocols worldwide. However insufficient supply, the rationale of use and distribution of vaccines in low income countries, the health condition of the participants in the trials, inclusion and exclusion criteria, the comparative arm, the inclusion of pregnant women, risks and benefits, the availability of the final product once trial is finished and the voluntary or compulsory character of immunization are some of the ethical issues that deserve consideration in the development and distribution of vaccines as a part of public health policies in low income countries.

  • Matthias Müllner
    Measles vector vaccine platform as an effective tool to prevent chikungunya virus infection
    Time: 12:15-12:40
    Speaker
    Matthias Müllner
    Themis Bioscience GmbH
    Austria
    Biography

    Matthias Müllner holds a Master’s degree in Molecular Biology from the University of Vienna and completed his Doctoral studies in 2010 at the Department of Virology and Biomedicine at the Veterinarian University of Vienna. He joined Themis Bioscience in 2011 and in his function as Head of CMC, he was responsible for the development of a stable and robust manufacturing process for Themis’ Measles based live virus vaccine platform technology. The respective process was successfully used to manufacture phase 1 and/or phase 2 clinical batches for vaccines against Chikungunya Virus (MV CHIK), Dengue Virus (MV DEN) and Zika Virus (MV ZIKA). Currently, the process is optimized for commercial vaccine production.

    Abstract

    Themis’ is developing a safe, effective and affordable preventive vaccine platform against priority pathogen diseases that have the potential to cause epidemics such as Chikungunya or Zika virus infection by using a “plug-and play” vaccine technology. This technology is based on a measles vaccine vector (MV) that can be easily genetically modified to express immunoprotective proteins for designated emerging infectious pathogens. This delivery platform technology has already demonstrated proof of principle in humans through a Phase 1 clinical trial in 42 healthy volunteers with a recombinant measles vaccine against Chikungunya virus (MV-CHIK). We showed that the vaccine was well tolerated. One immunization induced functional, neutralizing antibodies in up to 90% of immunized subjects, a second immunization induced 100% seroconversion. Importantly, immunogenicity was independent of pre-existing anti-vector (measles) immunity. We show here a Phase 2 clinical trial to demonstrate the vaccine vector safety and immunogenicity in up to 300 subjects. Preliminary findings point at excellent safety and immunogenicity profile in the two doses tested. Data are currently under final evaluation and auditing, and will be presented here.

  • Geert Vanden Bossche
    Universally protective vaccines: A revolution in modern vaccinology
    Time: 13:30-13:55
    Speaker
    Geert Vanden Bossche
    German Cancer Research Center
    Germany
    Biography

    Geert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his Postdoctoral training in Virology, Immunology and Molecular Biology at the Free University of Berlin and the University of Hohenheim (Germany), he was given the Venia Legendi and subsequently held adjunct faculty appointments at the University of Hohenheim (Germany), the University of Leuven (Belgium) and the European Faculty for Environmental Sanitation at the University of Ghent (Belgium). He then transitioned to the Vaccine Industry to serve various senior roles in both early and late vaccine development (GSK, Novartis, Solvay). In 2008, he joined the Bill & Melinda Gates Foundation in Seattle to serve as Senior Program Officer in Vaccine Discovery for Global Health. Furthermore, he also founded UNIVAC LLC, a start-up vaccine company, and coordinated the Ebola Vaccine Program on behalf of GAVI. He is now the Head of Vaccine Development Office at the German Center for Infection Research (DZIF) in Germany. He is board certified in Virology and Microbiology, the author of over 30 publications, and inventor on a patent application for universal vaccines. He has presented vaccine- and adjuvant-related topics at multiple international congresses.

    Abstract

    To eliminate safety risks related to infectivity, inactivated pathogens and, more suitably, well-characterized pathogen-derived antigens (Ags) have increasingly been used as immunogens in ‘modern’ vaccines. The selection of these Ags is usually based on their capacity to induce immune responses that ‘correlate’ with natural protection. These Ags, however, are composed of antigenically variable or conformation-dependent epitopes (e.g., B cell epitopes) and/ or subject to immunogenetic restriction (e.g., linear, T cell epitopes). In addition, the immunogenicity of conventional vaccinal Ags is largely dependent on memory CD4+ T helper cells. However, activation of the latter upon natural infection or foreign Ag exposure of genetically predisposed subjects can occasionally lead to immune pathology. On the other hand, pathogens have evolved to incorporate into their arsenal of peptides self-mimicking motifs that are highly conserved and vulnerable as they are exposed on the surface of infected or pathologically altered host cells. These Ags, however, are either not immunogenic or subvert the host immune system. Hence, they are not used as vaccinal Ags in contemporary vaccines. We consider that new vaccines enabling immune targeting of these Ags by MHC-unrestricted memory NK cells are the new Holy Grail in modern vaccinology.

  • Sabrina Schrauf
    Live-recombinant measles virus vaccine to prevent zika virus infection
    Time: 11:25-11:50
    Speaker
    Sabrina Schrauf
    Themis Bioscience GmbH
    Austria
    Biography

    Sabrina Schrauf graduated as PhD from the University of Vienna in the fields of Virology where she worked on Flavivirusbiology (including Tick-borne encephalitis virus and West Nile virus). She joined Themis in 2015 to coordinate preclinical development of vaccines. (vaccine design and testing).

    Abstract

    Zika virus is an emerging mosquito-borne flavivirus. The virus emerged in the past 70 years only sporadically with self-limiting small outbreaks. In 2013, a large outbreak in French Polynesia resulted in over 30,000 cases. Since early 2015 Zika virus spread in the Americas and to date caused autochthonous, vector-borne transmission in 48 countries and territories. This rapid emergence of the previously unknown pathogen raised the urgent need for a vaccine that can be rapidly produced in response to a newly emerging pathogen. Themis took the challenge and developed a vaccine candidate from design to Phase 1 clinical trial within 14 months. The MV-ZIKA vaccine candidate is a live attenuated recombinant viral vectored vaccine for the prophylaxis of Zika virus infection. The measles virus (MV) Schwarz vaccine strain was used as the backbone into which nucleotide sequences encoding Zika virus structural proteins glycoprotein precursor (prM) and the Envelope (E) were inserted to produce the MV-ZIKA. In measles virus susceptible mice, single or multiple vaccinations with MV-ZIKA induced a robust protective immunity, as shown by the induction of ZIKV E protein specific antibodies. The immunization of Cynomolgus macaques resulted in the induction of Zika virus neutralizing antibodies in all vaccinated animals. To evaluate the optimal dose of MV-ZIKA regarding immunogenicity, safety, and tolerability we initiated a double blinded, randomized, placebo-controlled, multi-center, phase 1 trial in 48 healthy volunteer subjects. The subjects will receive one or two vaccinations. The immunogenicity as confirmed by the presence of functional antibodies will be determined on day 28 after the second immunization. The clinical trial is currently ongoing and preliminary data will be presented here.

  • Thomas Lehner
    A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection
    Time: 14:20-14:45
    Speaker
    Thomas Lehner
    Kings College London
    United Kingdom
    Biography

    Dr Thomas Lehner, Professor of Basic and Applied Immunology; London University. Qualifications: MB, BS London, MD London, FDS RCS, FRC Path, F Med Sci Prizes and Honours Besredka Prize of the Pasteur Institute, Lyon, France. Honorary Doctorate, Karolinska Institute, Stockholm, Sweden Honorary Life President of the International Society for Behcet’s Disease Appointed Commander of the British Empire (CBE) Honorary Fellow of the Royal Society of Medicine Selected International appointments Member of NIH (NIAID), Bethesda US Review Committee Research Grants 1999-2007. Member of Scientific Committee of the International Mucosal Immunology 1997-2006 Member of the Scientific Committee of the Institute of Virology of the University of Maryland (1998-2002). Research Career A total of 265 peer-reviewed papers published in scientific journals. Over the past 20 years research carried out in animals and humans, preventing HIV and SIV infections. Focussed on mucosal immunisation, generation of CC-chemokines, CCR5 coreceptors stress agents and alloimunisation. Major research grants from the MRC, NIH, European Union, Gates Foundation.

    Abstract

    HIV infection affects 37 million people and about 1.7 million are infected annually. Only the RV144 vaccine phase III clinical trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these two critical functions of the vaccine we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4+ T cells and they were further characterized into 4 subsets. These consisted of IL-2/IL-15 receptors and APOBEC3G anti-viral restriction factors, which were upregulated, whereas CCR5 co-receptors and ?4?7 mucosal homing integrins were decreased. A parallel increase in CD4+ T cells was recorded of the IL-15 receptors, APOBEC3G and CC chemokines, with a decrease in CCR5 expression. We suggest a novel mechanism of dual memory stem cells; the established sequential memory pathway, TSCM ?Central ?Effector memory CD4+ T cells and the innate pathway consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by endogenous HSP70, the hallmark of cellular stress. The memory stem cells and innate immunity pathways should be optimized to boost the efficacy and immune memory of protection against HIV-1. TSCM are likely to be activated by inducible HSP70, as PES (phenylethynesulphonamide), a small molecular inhibitor induced a dose-dependent inhibition of TSCM. The link between memory stem cells and innate immunity suggests a novel mechanism of inhibiting HIV-1 acquisition, by decreasing CCR5 and ?4?7, increasing IL-15/IL-2 receptors and HIV-1 restriction factors.

  • Emmanuel Drouet
    Challenges and dilemmas about vaccines against Epstein Barr virus and the other herpesviruses
    Time: 14:45-15:10
    Speaker
    Emmanuel Drouet
    University of Grenoble-Alpes
    France
    Abstract

    Human Herpesviruses (HHV1-8) have co-evolved through a persistent infection in the host, spread efficiently to others, generally without causing serious disease. The complex interplay between host and virus has made it difficult to elaborate useful vaccine strategies to protect against the HHV-associated diseases. The Varicella-Zoster vaccine represents the paradigm of a successful Herpesvirus vaccine. This live-attenuated vaccine demonstrates unequivocally that it is possible to develop vaccines against these viruses. Over the years, the development of HHV vaccines has been a story of mixed fortunes, especially for HSV-2 and HCMV. However, studies carried out in various disease settings (i.e. transplant patients or pregnant women), have clearly emphasized the importance of cellular immunity and it is indeed encouraging to see that recent HHV vaccine (i.e. HCMV) development programs have started to incorporate this arm of the immune system. Nowadays, an array of arguments calls for a realistic goal for vaccine strategies which should be preventing HHV disease rather than HHV infection. It is particularly the case for the Epstein-Barr Virus (EBV or HHV4) which is the primary cause of infectious mononucleosis and is associated with epithelial cell carcinomas, as well as lymphoid malignancies. One challenge is that the EBV expresses very different proteins during its lytic and its latent phases. To address this, vaccine candidates have been designed to include proteins from both phases. Here we review the history of EBV vaccine development and the current strategies in the development of new EBV vaccines: As EBV is associated with nearly 200,000 new malignancies each year worldwide, an EBV vaccine to prevent these diseases is really needed. Parallel to this need one could propose priorities for future research: (i) identification of surrogate markers that predict the development of EBV-related malignancies. (ii) definition of a goal for an EBV vaccine and criteria for licensure.

  • Youness Cherradi
    Development of a production and purification platform for virus like particles (VLP) and adenovirus vector vaccine candidates: two case studies
    Time: 15:30-15:55
    Speaker
    Youness Cherradi
    Merck Life Science, Process Solutions, Belgium
    Belgium
    Biography

    Youness Cherradi, PhD is a Process Development Scientist for Merck in EMEA since 2013. He is responsible for customer process development and optimization on various downstream technologies and recently took the responsibility of Global Lead for the Vaccine Process Development team at Merck. He completed Master’s Degree in BioEngineering, specializing in Chemical Engineering, Biotechnologies and Applied Genetics from the Université Libre de Bruxelles (ULB, Belgium) as well as a PhD in Molecular Bacteriology from the Medicine Faculty of ULB where he worked and published on virulence mechanisms of Type-3 Secretions Systems.

    Abstract

    Youness Cherradi, PhD is a Process Development Scientist for Merck in EMEA since 2013. He is responsible for customer process development and optimization on various downstream technologies and recently took the responsibility of Global Lead for the Vaccine Process Development team at Merck. He completed Master’s Degree in BioEngineering, specializing in Chemical Engineering, Biotechnologies and Applied Genetics from the Université Libre de Bruxelles (ULB, Belgium) as well as a PhD in Molecular Bacteriology from the Medicine Faculty of ULB where he worked and published on virulence mechanisms of Type-3 Secretions Systems.

Day 2

KEYNOTE SPEAKERS
  • Translational Vaccinology: A myth?

    German Center for Infection Research (DZIF), Germany
    Germany
    Biography

    Geert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his Postdoctoral training in Virology, Immunology and Molecular Biology at the Free University of Berlin and the University of Hohenheim (Germany), he was given the Venia Legendi and subsequently held adjunct faculty appointments at the University of Hohenheim (Germany), the University of Leuven (Belgium) and the European Faculty for Environmental Sanitation at the University of Ghent (Belgium). He then transitioned to the Vaccine Industry to serve various senior roles in both early and late vaccine development (GSK, Novartis, Solvay). In 2008, he joined the Bill & Melinda Gates Foundation in Seattle to serve as Senior Program Officer in Vaccine Discovery for Global Health. Furthermore, he also founded UNIVAC LLC, a start-up vaccine company, and coordinated the Ebola Vaccine Program on behalf of GAVI. He is now the Head of Vaccine Development Office at the German Center for Infection Research (DZIF) in Germany. He is board certified in Virology and Microbiology, the author of over 30 publications, and inventor on a patent application for universal vaccines. He has presented vaccine- and adjuvant-related topics at multiple international congresses.

    Abstract

    To be updated

  • Accelerating vaccine process development and manufacturing: innovative approaches and challenges

    EMEA chez Merck Group
    France
    Biography

    Dr. Anissa Boumlic-Courtade is the Associate Director for the vaccine initiative in EMEA with Process Solutions division of Merck Life Sciences. Dr. Boumlic-Courtade joined Merck in 2009 and has held various positions focused on downstream processing, virus safety, and monoclonal antibody and vaccine manufacturing. Dr. Anissa Boumlic-Courtade holds a M. Sc. in Biotechnology Engineering from the Ecole Supérieure de Biotechnologie (ESBS) de Strasbourg (France) as well as a Ph.D. in Molecular Biology and Biochemistry from the University of Strasbourg co-directed with the University of Thessaly (Greece).

    Abstract

    Preventable diseases vaccines save millions of lives but are not always delivered when needed to a large fraction of the population. In addition, there are a number of infectious diseases that still remain without cure or vaccine. Innovations in process development and manufacturing are unavoidable to enable release of existing and novel vaccines and their delivery where and when they are mostly needed. This presentation will outline where innovative approaches and technologies while developing and/or optimizing the process and at manufacturing scale can accelerate clinical phases and compress the time to market of highly needed vaccines. Furthermore, using case studies like Ebola and influenza outbreaks, challenges will also be highlighted in pandemic situations and approaches will be discussed on how to alleviate roadblocks and be better prepared to manufacture vaccines in urgent situations.

Novel Vaccines - Development and production | Vaccines formulation
Speaker
  • Camille Locht
    A live attenuated nasal vaccine against pertussis
    Time: 11:25-11:50
    Speaker
    Camille LOCHT
    French National Institute of Health and Medical Research
    France
    Biography

    Dr. Camille Locht holds currently a position as Research Director at the French National Institute of Health and Medical Research (Inserm) and, since 2010, is the founding director of the Center for Infection and Immunity of Lille on the campus of the Institut Pasteur de Lille in France. He has obtained his PhD at the Catholic University of Leuven in Belgium in 1984. After a 3-years post-doctoral stay at the National Institute of Allergy and Infectious Disease in the USA, where he started to work on pertussis and cloned the pertussis toxin genes, he joined SmithKline – Beecham (now GSK) to help developing acellular pertussis vaccines. Since 1989 he is the head of a research laboratory at the Institut Pasteur de Lille, where he has been the Scientific Director from 2002 to 2013. His research interest is in molecular pathogenesis of respiratory infections, essentially pertussis and tuberculosis, with the long-term aim to develop new tools to combat these diseases. A very powerful molecular typing system for mycobacteria, invented in his laboratory has already reached the market, and a live attenuated nasal pertussis vaccine developed in his laboratory has now successfully completed phase I clinical trials and is currently in clinical development. He also has discovered a protective mycobacterial latency antigen, called heparin-binding haemagglutinin (HBHA), which is now in late stage pre-clinical development as an anti-tuberculosis vaccine candidate. He has authored more than 300 international publications, book chapters and patents and has obtained several research awards.

    Abstract

    Pertussis or whooping cough is making a dramatic comeback in several countries, especially since the switch from the first-generation whole-cell to the more recent acellular vaccines. The reasons for this resurgence are still under debate, but may essentially be due to unexpectedly fast waning of acellular vaccine-induced immunity and insufficient effectiveness of these vaccines to protect against infection by Bordetella pertussis, the principal causative agent of whooping cough, even though they protect effectively against pertussis disease. To ultimately control pertussis, new vaccines are necessary that protect both against the disease and B. pertussis infection. We have developed a live attenuated pertussis vaccine that can be administered by the nasal route. This vaccine, named BPZE1, has been shown to be safe in pre-clinical animal models, including severely immunocompromised mice, and to induce strong antibody and T cell responses. A single nasal dose of BPZE1 was able to protect mice against challenge with virulent B. pertussis, and protection was significantly longer lived than that induced by multiple administrations of acellular vaccines. In non-human primates, BPZE1 was also found to be safe and to protect against disease and infection caused by a highly virulent B. pertussis clinical isolate. BPZE1 has now successfully completed a phase I clinical trial in humans and was found to be safe in adults, to be able to colonize transiently the human respiratory tract and to induce immune responses in the colonized individuals. The vaccine is now undergoing further clinical development. Interestingly, in the course of the preclinical investigations, unexpected immunomodulatory properties or BPZE1 were uncovered. Without being immunosuppressive, BPZE1 appears to be anti-inflammatory and to protect mice against influenza virus-induced death, against experimental asthma and against experimental hypersensitivity of the skin, most probably linked to innate immune responses induced by the vaccine. Together with the protective effects against B. pertussis infection, these anti-inflammatory properties make BPZE1 an interesting tool for the benefit of public health, far beyond the control of pertussis.

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