Vaccine-induced mouse antibodies targeting Plasmodium falciparum PfVFT antigen inhibit blood stages through multiple mechanisms.

While vaccines are central to eradicate malaria, they remain elusive, with numerous malaria vaccine candidates showing limited efficacy in Phase II and III studies. Controlled human malaria infection studies have showed that human volunteers, immunized with Plasmodium falciparum sporozoites under drug cover, were protected experimentally from a subsequent challenge. Here, to identify new targets associated with protection, we utilized a previously developed screening approach, where we screened sera from protected and non-protected individuals against newly included hypothetical antigens in a P. falciparum antigen library. PfVFT1 was found to be associated with protection, with antibodies against PfVFT1 being detected in all protected individuals. We found that vaccine-induced mouse anti-PfVFT sera inhibited parasite reinvasion into RBCs, promoted complement deposition to induce parasite lysis, and supported phagocytosis and antibody-dependent cellular inhibition of the parasite. Together, these data indicate that PfVFT1-specific antibodies can engage multiple effector mechanisms relevant to antimalarial immunity.