Placental Malaria (PM) constitutes a major health problem. Globally, it is estimated that at least 25% of pregnant women are infected with malaria which attribute to more than 20% of all maternal deaths in malaria endemic areas. Malaria infection during pregnancy accounts for over 50,000 maternal and 200,000 neonatal deaths annually. Prevention of placental malaria currently relies on long lasting insecticide treated nets and intermittent preventive treatment during pregnancy (IPTp). These interventions however only offer partial protection. The development of an effective vaccine could therefore be an attractive tool to control PM on its own, or to complement the existing yet imperfect tools.
About the VAC4PM Project
The Global Health Innovative Technology Fund (GHIT Fund) facilitates international partnerships that bring Japanese innovation, investment, and leadership to the global fight against infectious diseases and poverty in the developing world. Financial support from the GHIT Fund has been secured by a consortium from Africa, Europe and Japan to advance placental malaria vaccine development. The VAC4PM project partnership, led by the European Vaccine Initiative (EVI), will strengthen its network and build on previously conducted pre-clinical and first-in-human (phase Ia/b) PM vaccine clinical studies in Europe and Africa, in collaboration with project partners from Ehime University (Japan), Inserm (France), University of Copenhagen (Denmark), Groupe de Recherche Action en Santé (Burkina Faso), Noguchi Memorial Institute for Medical Research (Ghana) and Institut de recherche pour le développement (France).
“Malaria in pregnancy is a severe disease that affects a particularly vulnerable demographic group, pregnant women. I am delighted that the GHIT Fund further supports the development of placental malaria vaccines, an intervention that is expected to greatly impact on morbidity and mortality of pregnant women and infants.” says Ole F. Olesen, Executive Director of EVI.
The two vaccine candidates PAMVAC and PRIMVAC have previously been assessed head-to-head in non-human primate immunogenicity studies and both have undergone independent phase I clinical trials using harmonised procedures. The clinical trial results demonstrated that both adjuvanted vaccine candidates are safe and well-tolerated and induce good homologous immune responses. Clinical trial data and animal immunisation results show lasting immune responses, confirming the feasibility of developing a PM vaccine .
Each vaccine candidate, PAMVAC and PRIMVAC, consists of a single recombinant protein using similar but complementary approaches. However, VAR2CSA is a diverse antigen, and it is therefore essential to optimise the cross-reactivity against different VAR2CSA variants and to further evaluate the longevity of the immune response, prior to embarking on costly, large scale phase II clinical trials. This project therefore seeks to further characterise the longevity of the PRIMVAC-induced immune response in women in malaria-endemic areas, as well as the capacity of the vaccine to boost and broaden a natural acquired immune response. Another aspect of the project is to undertake the pre-clinical development of PAMVAC-CLP. PAMVAC-CLP is an improved version of PAMVAC, where a capsid-like particle (CLP) has been added as backbone, potentially improving immunogenicity, cross-reactivity and longevity of the induced immune response.
PRIMVAC and PAMVAC-CLP together with its variants in early pre-clinical evaluation, constitute a promising portfolio of PM vaccine candidates.
European Vaccine Initiative (EVI), Designated Development Partner, is a not-for-profit Product Development Partnership (PDP) that supports the development of safe, effective and affordable vaccines for global health. Since its inception in 1998, EVI worked closely with partners and donors worldwide to move more than 40 vaccine formulations forward.
EVI operates as an independent, science-driven organisation, leading innovative solutions while supporting vaccine R&D in a disease-overarching manner through cross-cutting activities, capacity strengthening and advocacy.
Consortium: European Vaccine Initiative (EVI) will be responsible for overall coordination and management, oversee clinical trial activities, and lead in protocol development. Ehime University (Ehime) will produce a variety of genetic variants of VAR2CSA to investigate the level of cross-reactive antibodies induced by vaccination. University of Copenhagen (UCPH) will be responsible for vaccine manufacture and development of the CLP-PM formulation for pharmaco-toxicology studies. Inserm, inventor of the PRIMVAC vaccine, will provide the PRIMVAC vaccine candidate and will further perform the functional immunological characterization and statistical analyses for the PRIMVAC studies. The Groupe de Recherche Action en Santé (GRAS) will conduct the phase Ib follow-up study of the PRIMVAC-vaccinated women and will perform the phase Ib booster study. The Noguchi Memorial Institute for Medical Research in Ghana/Institut de recherche pour le développement (IRD) will be involved in the preclinical characterization of the vaccine candidates with the aim to increase cross-reactivity of the vaccines, and the immunological characterization of human samples.
Quick facts about VAC4PM:
Start Date: 25/10/2021
End Date: 30/09/2023
Funder: Global Health Innovative Technology Fund
Grant number: G2020-214
Total Funding: 469,292,404 JPY (approx. €3.6 Mio)
Designated Development Partner: European Vaccine Initiative (EVI)
EVI Communication Team
 https://clinicaltrials.gov/ct2/show/NCT02658253  https://clinicaltrials.gov/ct2/show/NCT02647489  Mordmüller B et al. Clin Infect Dis. 2019 Oct 15;69(9):1509-1516  Sirima SB et al. Lancet Infect Dis. 2020 May;20(5):585-597