EVI Rendez-Vous 2015 Summary
The European Vaccine Initiative (EVI) “Rendez–Vous” fifth edition took place on the 9th December 2015 at Institut Pasteur Paris, France. Attendees included stakeholders from various European countries, United States of America (USA), Asia and Africa, and included members of EVI’s governing bodies, funders, research partners, and the EVI Secretariat. 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 lively discussions and questions.
The meeting was opened by Claude Leclerc of Institut Pasteur Paris who emphasised the complementarities of EVI and Institut Pasteur’s on research and development (R&D) of vaccines against diseases of poverty, and thanked EVI for its long standing contribution to vaccine research, and more specifically in securing funding for clinical trials. She also made reference to the recent tragic attacks in Paris, and noted that it was rewarding that participants had attended regardless, and called upon them to continue the fight against diseases of poverty through innovation and education, as well as by promoting development of strong international collaboration for a peaceful world.
EVI Executive Director, Odile Leroy, thanked all participants for coming, and took the opportunity to thank Dr Aissatou Toure, and Prof Sam McConkey for their commitment during six years as members of EVI’s independent Scientific Advisory Committee (EVI SAC), and to remind the audience of their critical contribution to the development and expansion of EVI since its inception. She was also pleased to announce that Regitze Thøgersen former programme manager at EVI for eight years, had now chosen a new challenge in her carrier, and she expressed great appreciation of the quality of the work done by Regitze. She reminded participants that the purpose of the EVI Rendez-vous, open forum was to review the progress of EVI’s portfolio, and to support the independent assessment of EVI projects by the Scientific Advisory Committee. Odile Leroy drew attention to a few of EVI’s many successes, including the strategy to combine phase Ia and phase Ib, as used for P27A and AMA1-DiCo malaria vaccine candidates, and the bringing together of top researchers in placental malaria from Denmark, France and the USA. EVI is planning to use the same accelerated approach for the placental malaria vaccine candidates with phase Ia in Europe and phase Ib in sub-Saharan Africa. EVI is active in vaccine development from pre-clinical activities to early clinical development, with a strong focus on harmonisation of vaccine development activities when feasible. Pre-clinical activities are currently diversified into universal influenza, paratyphoid, dengue, and malaria vaccine research.
The key note speaker, Matthieu Perreau, discussed the importance of helminths with regard to poverty related diseases (PRDs). The IDEA project is a joint project aiming at analysing the effect of helminths on malaria, HIV and TB. Matthieu Perreau reported that in a study on TB, helminths led to skew to Th2 instead of Th1. The impact of helminths on modulation of responses has been assessed with intracellular flow cytometry and Luminex in Tanzania and South Africa, showing no impact in Tanzania, while in South Africa TB patients with worms generally had more Th1 responses. Memory CD4 T cells were more numerous in Tanzanians compared with South Africans, hence the need for Luminex results to better understand the differences. All helminths appear to skew to Th2 irrespective of the type or number. The issue of antigen load is being investigated. A pilot study on HIV showed no skewing to Th2, and that CD4 levels are not influenced by helminths. Discussions are on-going on assessment of transcription factors and the effect of treatment of worms which was not assessed.
David Wyllie presented BELLEROPHON project. Staphylococcus aureus varies from inducing minor to life-threatening conditions and is virtually universal. Protection is difficult to assess and a challenge model for vaccine assessment is being tested. Another difficulty is that a previous vaccine candidate resulted in adverse outcomes and increased mortality in vaccinees. Carriage effect on humans and cellular risk factors are yet to be identified. The project is now increasingly focussing on one antigen discovery for a S. aureus new vaccine candidate.
Ed Remarque presented the EDUFLUVAC approach, which is to perform epitope dilution for flu antigens using Virus-Like Particles (VLPs) to stimulate B cells capable of producing broadly neutralising antibodies. To cover all strains of influenza two approaches were used: coverage of seasonal strains and coverage by unknown pandemic strains by epitope diluted in VLP. A polyvalent with five flu strain VLPs was compared with the monovalent VLPs. There were antibody response yields for all five components, despite a low amount of antigen. Ed Remarque brought participants’ attention to the similarity between AMA1-DiCo and EDUFUVAC vaccine candidates, and explained how to cover the diversity for influenza vaccines. Expanded coverage for pandemics and seasonal coverage is the main line of this approach.
The two placental malaria vaccine candidates PAMVAC and PRIMVAC were presented.
Morten Nielsen presented the PAMCPH and PlacMalVac projects, showing promising adjuvant selection for PAMVAC vaccine candidate. The minimal binding region has been identified called FRC3 (ID1-DBL2x-ID2a, and good manufacturing practice (GMP) production completed. The vaccine will enter clinical trial in early 2016 in Germany (phase Ia) and Benin (phase Ib).
Sophie Hallez and Benoit Gamain from PRIMALVAC project presented the pre-clinical activities and GMP production data for PRIMVAC vaccine candidate. Successful technology transfer from GTP technology to Novasep has been demonstrated. Production was carried out in accordance with international regulations. A single Plasmodium falciparum clone induces broadly neutralising antibodies. The PRIMVAC clinical trial will start in early 2016 in France (phase Ia) and Burkina Faso (phase Ib).
Patrick Duffy presented the placental malaria animal model (PlacID) project. The aim is to find a model to assess placental malaria vaccine candidates. The placental malaria vaccine candidate from the Laboratory of Malaria Immunology and Vaccinology, and PAMVAC and PRIMVAC will be tested using this placenta malaria model.
Harmonisation and standardisation is seen by EVI as being highly beneficial and hence EVI’s reason for being involved in projects dedicated to harmonisation and its implementation in all EVI core projects.
Emanuele Montomoli presented the standardisation and development of assays for assessment of influenza vaccine correlates of protection (FLUCOP). The main objective is to improve and standardise existing immunological assays, and to develop a tool-box of standardised, validated serological assays to better evaluate efficacy of future seasonal human influenza vaccines, which will impact on the R&D process in future influenza vaccine research.
Othmar Engelhardt presented the harmonisation work done in EDUFLUVAC. There are many concepts underlying universal influenza vaccine candidates that require several assays to evaluate the immune response. High priority should be given to primary evaluation criteria for novel vaccines, with exploratory assessments performed early in development to define the immune profile. There is also a need to validate assays from antigen discovery to clinical trial.
Andrew Pollard presented the first human model established during the paratyphoid infection model (PIM) project to accelerate the development of paratyphoid vaccines. The Oxford Vaccine Group demonstrated - with the first ever safety and feasibility study of human challenge of Salmonella Paratyphi A - that it is safe and well tolerated.
EVI achievements now lead the introduction of vaccine candidates into clinical development. The results of the first clinical trials of malaria vaccine candidates are now available and promising.
Simon Draper presented the development of the RH5 based vaccine candidates. The phase Ia clinical trial of MultiMalVax with AdCh63 and MVA vaccine candidates shows promising results for the prime boost approach. The protein based vaccine candidate that emerged from InnoMalvac project has been further produced in Drosophila S2 stable cell line expression system, and is now being tested adjuvanted in phase Ia clinical trial.
Jean-Baptiste Yaro presented the results of the phase I/IIb clinical trial of ME-TRAP in the Burkina Faso pilot study under the MVVC project. The vaccine candidate is safe and well tolerated, but has no significant efficacy against clinical malaria. However, possible efficacy against severe malaria after one year follow-up was noted.
Victorine Mensah highlighted the successful South-South collaboration between Université Cheick Anta Diop (Dakar, Senegal) and Medical Research Council (MRC, The Gambia) with beneficial experience sharing and capacity building as part of MVVC2 project. The phase Ib clinical trial showed high immunogenicity in infants and neonates in the entire group, and a higher ELISpot response when boosted by MVA was observed in older children. The ME-TRAP liver stage vaccine candidates undergoing clinical trial are safe and well tolerated.
Adrian Hill presented the multi-component (four-stage, sporozoite, liver, blood and transmission blocking) malaria vaccine strategy developed for MultiMalVax project. The phase Ia clinical trials of the liver and transmission blocking stage vaccine candidates are ongoing. The next step will be the selection of the antigens for the multi-component vaccine candidate.
The consortium developing the P27A vaccine candidate, represented by Claudia Daubenberger, Francois Spertini, and Salim Abdulla presented initial results of the phase Ia/Ib in healthy adults (25-49 years old). P27A vaccine candidate has a good humoral response. It is driving a stronger proliferation of CD4+ T cells in adults that received GLA-SE. A successful North-South capacity and competency transfer speeded up the development of P27A considerably. All samples were analysed in Tanzania.
Christine Durier presented the AMAI-DiCo phase Ia/Ib malaria vaccine trial implemented in France and Burkina Faso, using two adjuvants (GLA-SE and alhydrogel). Primary results show that AMA1-DiCo induces antibodies with both adjuvants. Further exploratory functional analyses will be performed to confirm the higher antibodies titers.
Toshihiro Horii presented the SEmalvac clinical trial in Burkina Faso. The first cohort (25-60 months) was recruited in June 2015. Seven days after vaccination there were no serious adverse events, and the vaccine was well tolerated. The independent data safety monitoring committee recommended starting recruitment of the second cohort in September 2015.
Anne Wajja presented the effects of helminth infection during a phase II clinical trial of a booster tuberculosis vaccine candidate in adolescents in the IDEA project. The hypothesis is that worm infection contributes to the low efficacy of BCG vaccine. The ELISpot results at day 56 suggested a more sustained response among those with Schistosoma mansoni than those without helminths. These results have to be confirmed using Luminex and antibody assays.
Vaccine research’s major leaders and stakeholders agreed to develop the first roadmap for future European vaccine R&D with a unique vision. This work, done under the IPROVE project, was presented by Michael Watson. There is a need to maintain and sustain investment in basic and fundamental science underpinning vaccines research. The roadmap will be launched in March 2016.
Odile Leroy unveiled the new EVI strategic plan for 2016-2020, the development of which was led by Mansour Yaich. The plan provides an opportunity to further pool resources, maximise synergies and built partnerships with other players in the vaccine R&D field, including other product development partnerships, national networks of vaccine researchers, research infrastructures, and the vaccine industry. Odile Leroy highlighted the successes of EVI which include 23 phase I clinical trials with three vaccines tested in phase II in Africa. The EVI portfolio has diversified as has its donors. Other results include strengthened partnership, and capacity building both in Africa and Europe. EVI is championing the discovery of antigens for diseases of poverty including malaria, and their introduction into early stages of clinical development. Moreover, the harmonisation of practices remains a priority for EVI as does support for an animal model platform, and alternatives to animal testing. In the coming five years, EVI aims to bring up to five candidate vaccines into clinical trials and facilitate engagement with industry to accelerate the delivery of safe, effective and affordable vaccines.
In his closing remarks, Clemens Kocken, Chair of the EVI-EEIG Board thanked all speakers and other participants for their contribution and the EVI Secretariat for organising the meeting.
More information on each project can be found under the project index.