Pan-African hybridization of PfSPZ increases antigenic diversity and replicative capacity for malaria vaccine design.

Plasmodium falciparum sporozoite (PfSPZ) vaccines, composed of aseptic, purified, live parasites that arrest during or just after liver-stage development, show excellent safety and efficacy in humans. They can induce complete protection against Pf infection, mediated primarily by cellular immune responses against parasite antigens expressed in hepatocytes. Current PfSPZ vaccines rely on the West African PfNF54 parasite, which uniquely produces high numbers of PfSPZ in mosquitoes, facilitating manufacturing efficiency. However, PfNF54 has relatively low hepatocyte infectivity, limiting potency. We created hybrid pan-African Pf strains by genetically crossing PfNF54 with East African Pf strains. The hybrid, AV27, was selected for development based on balanced contribution of parental genomes, high PfSPZ production, and high liver-stage infectivity. As compared with NF54-based PfSPZ vaccines, we expect AV27-based vaccines will have greater and broader efficacy at lower doses due to higher liver-stage infectivity and inclusion of unique East African CD8+ T cell epitopes.