EVI Rendez-Vous, 3 December 2014

2014

 EVI Rendez-Vous 2014 report

On 3rd December 2014 the annual review of EVI portfolio took place, for the first time at Institut Pasteur Paris, France.  More than 90 stakeholders, comprising governing bodies, funders, research partners and the EVI Secretariat, came together for an update on project progress and research findings.  The topics covered an overview of the EVI portfolio, specifically preclinical-, clinical- and harmonisation activities.

In his welcome speech, Christian Brechot, President of Institut Pasteur, Paris highlighted the importance of vaccine research with a reference to Institut Pasteur’s history of vaccination, and the strategy to further reinforce this research field. 

Odile Leroy, Executive Director, EVI and Alister Craig, chair of EVI’s Scientific Advisory Committee, stressed the important role of EVI in the development of vaccines against diseases of poverty, supporting partners in process development, regulatory submission, and early phase clinical development, including  harmonisation of laboratory assays, and clinical development, with EVI acting as ambassador between the various stakeholders.  EVI is instrumental in creating access to technologies that are crucial to vaccine development, and in advocating the need for funding of vaccine development, that helps to bridge the translational gap.  EVI’s work across diseases is illustrated by the diversification of EVI’s portfolio, with two new targets, paratyphoid vaccine (PIM) and universal influenza vaccine (EDUFLUVAC), as well as a new technology IMX313, an immune-enhancing antigen, which is being assessed for a Staphylococcus aureus vaccine (BELLEROPHON).

The pre-clinical work carried out under the BELLEROPHON project, to select the most promising antigens to be included in the S. aureus vaccine candidate, was presented.  The choice of the challenge model was also discussed with the audience, as it will be fundamental for the evaluation of the vaccine efficacy.

Through its involvement in the EDUFLUVAC and FLUCOP projects, EVI has broadened its scope to include the field of influenza vaccine development.  The activities implemented at Instituto de Biologia Experimental Tecnológica (iBET), to optimise the production and purification of influenza Virus-Like Particles (VLPs), were presented.  Indeed, robust and scalable manufacturing strategies need to be put into place to ensure the cost-effectiveness of VLP-based vaccines.  The VLP influenza vaccine candidates are currently being tested in mice, and their efficacy will then be evaluated in ferret and non-human primate challenge models.  EVI’s longstanding experience in immunoassay harmonisation for malaria vaccine candidates will be instrumental in FLUCOP.  This private-public consortium, coordinated by Sanofi and University of Siena, aims at standardising existing immunological assays, and at developing new tools to better evaluate efficacy of future seasonal human influenza vaccines.

Updates were presented by the two leading groups working on the development of placental malaria vaccine candidates.  In PRIMALVAC, the 3D7 DBL1-2 domain is expressed in a bacterial expression system, and process development was concluded with good yield and more than 99% purity of the recombinant protein.  The process was successfully transferred to a contract manufacturing organisation (CMO) for production of the vaccine candidate under good manufacturing practice (GMP) conditions.  The GMP manufactured recombinant protein is expected to be available in Q1 2015 with an envisaged start of the clinical trial in the second half of 2015.  Timelines and progress for PAMCPH/PlacMalVac are similar, and the projects are running head-to-head.  The University of Copenhagen team is, however, expressing the FCR3 ID1-DBL2-ID2 vaccine candidate in insect cells.  GMP manufacturing and clinical trial planning are on-going.  Placental malaria vaccine development is heavily funded by the Federal Ministry of Education and Research (BMBF) through KfW, the European Commission (EC) and Irish Aid.

EVI is also coordinating and partnering in several EDCTP funded projects, and the session was introduced by Jean Marie Habarugira (EDCTP) who briefed on the launch of EDCTP 2 on 02 December in Cape Town, South Africa.  A call for EDCTP-TDR fellowships is currently open, which includes three (3) fellowships for researchers from low- and middle-income countries to work at EVI.  Further calls will be launched shortly.

The Malaria Vectored Vaccines Consortium (MVVC) coordinated by EVI) is assessing a liver stage malaria vaccine candidate ME-TRAP in a viral vectored prime-boost strategy.  The vaccine candidate has shown to be safe in a phase Ib/IIb clinical trial in 700 Burkinabe children and infants.  The clinical trial was completed in October 2014 and the efficacy results are expected within the next six (6) months.  The study was performed at a centre in Banfora that has benefitted from MVVC capacity building activities over the past five years.

Under the MVVC 2 project that is coordinated by EVI, a phase Ib clinical trial is on-going to assess the safety and immunogenicity of ME-TRAP in a viral vectored prime-boost strategy co-administered with the enhanced programme on immunization (EPI) vaccinations in Gambian infants, which has proved to be safe in the first two groups.   It was highlighted that this clinical trial is a true South-South collaboration between the Medical Research Council Unit in the Gambia and the Université Cheikh Anta Diop, Senegal.  The importance of the development of alternative informed consent procedures using multimedia tools was mentioned, especially for countries with low literacy.

The MultiMalVax project is aiming to target all four life-cycle stages of the malaria parasite in the human host via the development of a multi-stage multi-antigen vaccine.  The first combination trial was conducted showing enhanced efficacy when combining the ME-TRAP vectored vaccine candidate with the RTS,S vaccine candidate from GSK.  The manufacture of a transmission blocking vaccine candidate and an alternative sporozoite vaccine candidate are on-going, and are expected to enter clinical trial in Mid-2015.

The latest successes in the development of the Rh5 blood malaria vaccine candidate, both in viral vectors (MultiMalVax) and as a recombinant protein (InnoMalVac), were presented.  A phase Ia clinical trial with a RH5 ChAd63-MVA prime boost strategy successfully started in Q3 2014.  Process development optimisation and immunogenicity studies in animal models with the recombinant Rh5 protein are currently on-going.

An update on the two phase Ia/Ib clinical trials with the blood stage vaccine candidates (AMA1-DiCo and P27A) were presented.  Both clinical trials have transitioned to Africa with a phase Ib stage and vaccination phase due to end early 2015.  The fast track clinical development strategy, an innovative approach developed by EVI in collaboration with the European and African clinical teams, has allowed testing of the vaccine in the targeted population early in the clinical development.

Understanding the impact of helminth infection on malaria epidemiology and malaria vaccine efficacy is one of the objectives of the IDEA project.  The effect of worm co-infection on the efficacy of the GMZ2 malaria vaccine candidate and on the humoral and cellular immune response is being assessed in a phase IIb clinical trial conducted in Lambaréné, Gabon.  Final results are expected by end 2015.

The successful development of the first ever human paratyphoid infection model under the PIM project was presented.  Researchers from the University of Oxford were indeed able to establish the dose of Salmonella Paratyphi A required to induce an attack rate of 60-75% in healthy adult volunteers.  This model will provide a unique opportunity to evaluate the efficacy of novel vaccine candidates and identify potential correlates of protection, thus providing an early proof of the vaccine concept.

In his closing words, Alister Craig thanked all speakers and other participants for their contributions and the EVI Secretariat for organising the meeting.  The achievements of EVI would not be possible without the support of its funders, and the commitment of the Board, Board of Stakeholders and independent Scientific Advisory Committee members.  While many funding agencies are nowadays focussing on the translational agenda, discovery science is needed to guarantee that the pipeline receives adequate supplies.  Alister Craig closed by thanking EVI for the wonderful time on the EVI’s Scientific Advisory Committee, and in her laudatory speech Marita Troye-Blomberg thanked Alister for his many years of continuous support.

More information on each project can be found under http://www.euvaccine.eu/portfolio/project-index.