A vaccine that prevents P. falciparum malaria in pregnant women would save hundreds of thousands of lives each year. PM is caused by IEs that bind to the placental receptor CSA and sequester in the placenta, where they cause disease and potentially lead to death of the mother and her offspring. The primary target group for a PM vaccine is women prior to their first pregnancy. The vaccine should therefore be administrated to women before they become pregnant for the first time. This would include women of child bearing age wishing to get pregnant and pre‐puberty or early puberty girls. Therefore, the PM vaccine would have to induce a long-lasting immune response still protecting women when they get pregnant, even though the vaccination took place several years before. Following an extensive screening study, an antigen spanning the CSA-binding DBL1x-2x region of the 3D7-VAR2CSA variant was selected as the PRIMVAC vaccine candidate.
The PRIMVAC antigen, expressed in E. coli and adjuvanted with either Alhydrogel or GLA-SE, was subsequently transitioned to clinical development. The first-in-human phase I trial assessed the safety and immunogenicity of adjuvanted PRIMVAC in 18-35-year-old women (68 subjects) who were a) malaria naive in France or b) naturally exposed to P. falciparum and nulligravid in Burkina Faso. This trial is registered with ClinicalTrials.gov, NCT02658253. The results of the phase Ia/b clinical trials show that PRIMVAC adjuvanted with Alhydrogel or GLA-SE was well tolerated and induced a strong immune response in all vaccinated women, with the production of antibodies that persisted for more than one year . The antibodies were capable of both, recognizing the parasitic antigen on the surface of the IEs and inhibiting their adhesive capacity. Taken together, the study has shown that the vaccine has the capacity to trigger a lasting and potentially protective immune response in both French and Burkinabe women.
We recently received funding from the Japanese GHIT fund to further characterize the longevity of the PRIMVAC-induced immune response in women in Burkina Faso. We will also evaluate in a phase Ib study, the capacity of PRIMVAC to boost and broaden a natural acquired immune response in primigravid and multigravid women. Furthermore, in collaboration with European vaccine Initiative, we just obtained an EU Horizon grant (2022 – 2027) (Under Grant Agreement Negociation) notably to move forward PRIMVAC in a bridging Phase Ib/II study in two clinical sites in Africa. We are also currently working on a second-generation vaccine that could broaden the immune response against the different VAR2CSA variants.