The European Vaccine Initiative (EVI) “Rendez–Vous” sixth edition took place on the 14th December 2016 at Institut Pasteur Paris, France. The meeting was attended by stakeholders from various European countries, North America, Asia and Africa, including members of EVI’s governing bodies, funders, research partners, and the EVI Secretariat. Some participants followed the meeting via telephone conference. Scientists and vaccine developers involved in EVI projects presented project progress and research findings, highlighting one of the most important areas of EVI’s activities; translation of research on diseases of poverty vaccines, focusing on early stages from preclinical to clinical development through harmonisation. Presentations were followed by discussions and questions.
The meeting was opened by Mahamadou Ali Thera, University of Bamako Faculty of Medicine, Mali, the current chair of the EVI Scientific Advisory Committee (SAC).
EVI Executive Director Odile Leroy gave some insights in EVI’s fundraising activities and engagement, mentioning that EVI strives to further broadening the disease scope of EVI. Moreover, she informed the audience that two new projects have recently started - ZIKAVAX and SEmalvac2- and that EVI´s effort to mobilise resources for the strengthening of a European vaccine R&D infrastructure seem promising. For 2017, a number of opportunities for resource mobilisation have been identified, and EVI will continue to be engaged in continued advocacy for product development for diseases of poverty. Odile Leroy furthermore points out that core funding is more and more replaced by project-specific funding, obliging EVI to adjust its fund raising activities.
Sodiomon Bienvenu Sirima presented on behalf of the PRIMALVAC team. The PRIMVAC placental malaria vaccine candidate has been shown to be stable for 18 months, therefore the expiry date of the clinical lot could be extended. A phase Ia study has started in France in May 2016. As there was a positive safety evaluation, a phase Ib study arm could start in Burkina Faso in December 2016. Based on the outcome of this phase I trial, decisions will be taken in the coming months on the further development and phase II clinical trials.
Sophie Houard and Morten Nielsen gave an update on the PlacMalVac project. The PAMVAC antigen formulated with Alhydrogel®, GLA-SE or GLA-SQ was tested in a phase I clinical trial. The clinical trial is open labelled for the phase Ia arm conducted in Tübingen, Germany and double blinded for the phase Ib conducted at the Institut de Recherche Clinique du Bénin, Benin. All the subjects in Germany have been vaccinated and no serious adverse events were observed. The safety and ELISA results for the Tübingen cohort were presented. Finally, the plans for the future development of the vaccine and the next steps to phase II clinical trial were presented.
Nicola Viebig presented on behalf of Patrick Duffy and the team the placental malaria animal model (PlacID) project. The goal of the first study is to confirm that passive transfer of purified immune IgG from multigravid African women will protect pregnant Aotus monkeys from placental malaria after inoculation of blood stage P. falciparum parasites. In a second study, the goal is to assess the Aotus model of P. falciparum placental malaria as a platform for assessing placental malaria vaccine candidates. Both studies are ongoing and the full data analyses, including results from samples collected after pregnancy and placental malaria, are expected to be completed by Mid-2017. If validated, the model will accelerate placental malaria vaccine development by facilitating quicker down-selection of vaccine candidates and providing safety data in pregnant primates at pre-clinical stage.
Sodiomon Bienvenu Sirima presented the AMAI-DiCo project. The results of the phase Ia/Ib malaria vaccine trial implemented in France and Burkina Faso, using two adjuvants (GLA-SE and Alhydrogel®) were presented. The results show that AMA1-DiCo was safe and well tolerated both with Alhydrogel® or GLA-SE. However in naturally exposed population no increase in human response was observed. Further exploratory functional analysis results will be available in 2017.
Sophie Houard and François Spertini presented the P27A project. The results of the phase Ia/Ib clinical trial in healthy adults (25-49 years old) were discussed. The P27A vaccine candidate has a good safety profile, no serious adverse events were observed and the most frequent adverse event was pain at the injection site. The primary and secondary objectives were met and the combination of GLA-SE and P27A as the best formulation to go forward. P27A can proceed to a controlled human malaria infection phase IIa clinical trial when additional funding is available.
Sodiomon Bienvenu Sirima presented the SEmalvac and SEmalvac 2 projects. For SEmalvac 1 a phase Ib clinical trial was performed with BK-SE36 in children aged 25 – 60 and 12 – 24 months in Burkina Faso. The follow up of the cohorts is ongoing. Safety data on the 25 – 60 months cohort show that the vaccine is safe; no serious adverse events were reported and most adverse events were mild to moderate in intensity. The data on cohort 2 and a full clinical report will be available in 2017. For SEmalvac 2 the clinical development of BK-SE36 will continue with CpG as adjuvant. A phase Ib clinical trial in age deescalating population will be performed to assess safety and immunogenicity. The clinical trial protocol will be submitted to the Burkinabe Authorities in December 2016.
Adrian Hill presented the multi-component (four-stage, sporozoite, liver, blood and transmission blocking) malaria vaccine MultiMalVax project. Several clinical trials, phase I up to phase II, have been performed and are ongoing for the individual vaccine candidate antigens. Results from the sporozoite stage vaccine look promising, the blood-stage candidate showed to be safe but will require further development, the transmission blocking candidate showed to be safe and immunogenic and the pre-erythrocytic candidate showed efficacy in UK adults. A combination vaccine candidate clinical trial is on-going.
Frederic Tangy presented the MVDVax project. MVDVax is a measles based Dengue vaccine where dengue antigens are expressed in a measles vector. The vaccine aims at inducing both a humoral and cellular immune response and it is covering all four dengue serotype E-proteins. The vaccine is currently in pre-clinical development and is tested in a non-human primate study, so far with promising safety and humoral immunogenicity data. In a next step the efficacy of the vaccine will be tested in a non-human primate challenge model. Data is expected in the beginning of 2017.
Gerrit Koopman presented the EDUFLUVAC project. The project aims to develop an influenza vaccine that educates the immune system to recognise cross-reactive epitopes by diluting out the strain specific epitope (Epitope Dilution Phenomenon), using a combination of influenza hemagglutinin antigens delivered on virus-like particle. Mouse immunisation studies have been finalised and antibody responses analysed. Currently proof of concept studies in ferrets and non-human primates are ongoing.
Frédéric Tangy presented the ZIKAVAX project. ZIKAVAX is a new EVI project funded by the European Commission that aims to develop a measles based Zika vaccine. More specifically, the ZIKAVAX project aims at developing a safe, effective, and affordable preventive vaccine against Zika virus infection. To achieve this goal, ZIKAVAX will use a delivery platform technology based on a measles vector (MV) with demonstrated proof of principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Following antigen selection and expression, immunisation studies will be conducted with the Zika vaccine candidate in mice and in a non-human primates challenge model that will be developed by the consortium. The ultimate goal of ZIKAVAX is the demonstration of safety and immunogenicity of a recombinant measles-Zika vaccine candidate (MV-ZIKA) in adult volunteers in a phase Ia clinical trial.
Oliver Schraidt presented the BELLEROPHON project. BELLEROPHON aimed at developing a Staphylococcus aureus vaccine targeting cellular and humoral immune responses. The observed effects with the BCAP recombinant proteins were not prominent enough to proceed with development. Virally vectored TPA.BCA showed however good immunogenicity and some efficacy in animal models. Novel antigens were identified and proved very promising with good immunogenicity and also some efficacy in animal models. This project is still in the discovery phase.
Hilde Depraetere presented the VAC2VAC project. VAC2VAC is a new project in the EVI portfolio that is different from other EVI projects in that it is not targeting to develop a new vaccine. VAC2VAC stands for ‘Vaccine batch to vaccine batch comparison by consistency testing’ and has the objective to deliver a proof of concept of consistency approach for batch release testing of established vaccines using sets of in vitro and analytical methods. More specifically it is a wide-ranging collaborative research project funded by IMI2 which aims to develop and validate quality testing approaches for both human and veterinary vaccines using non-animal methods. The initiative aims to provide the data to support the “consistency approach” for quality control of established vaccines. The current quality control approach for final products relies on in vivo methods. To achieve their goal, the project partners will develop, optimise and evaluate physiochemical and immunochemical methods, cell-based and other assays for routine batch quality, safety and efficacy testing of vaccines. This will be done in collaboration and consultation with regulatory agencies. Ultimately, the project aims to develop tests and approaches that will allow acceptance of the “consistency approach” for existing vaccines by the regulatory agencies and thereby significantly reducing in the future the use of animals for batch testing in routine vaccine production.
As can be seen, the EVI portfolio has diversified. EVI’s main focus remains on the discovery of antigens for diseases of poverty and their introduction into early stages of clinical development. In addition to that, the harmonisation of practices remains a priority for EVI as does support for an animal model platform, and alternatives to animal testing.
More information on each project can be found under http://www.euvaccine.eu/portfolio/project-index.