Immunization with genetically attenuatedP. falciparumparasites induces long-lived antibodies that efficiently block hepatocyte invasion by sporozoites

Whole-parasite malaria vaccines have shown promise in clinical trials. We recently reported the first human trial of a malaria vaccine based onPlasmodium falciparumgenetically attenuated parasites (PfGAP). Herein we report for the first time thatPfGAP induces prolonged functional humoral responses in humans. Six volunteers were exposed to 5 bites ofPfGAP-infected mosquitoes followed by approximately 200 bites. Plasma collected from all volunteers 3 months after the last exposure efficiently inhibits invasion of hepatocytes byP. falciparumsporozoites. The level of inhibition observed is comparable to that attained using plasma collected after 4-5 intravenously administrations of high numbers of irradiated sporozoites, validating the potential ofPfGAP malaria vaccines. Our data highlight the role of antibody responses in pre-erythrocytic stages of human malaria, and suggests that to be protective, malaria vaccines might need to elicit long-lasting functional antibodies in addition to cellular responses.