Human sterile immunity to Plasmodium vivax malaria correlates with specific antibody response elicited by immunization with radiation-attenuated sporozoites

Abstract

Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the RTS, S vaccine. Similar advances in P. vivax (Pv) vaccination have been elusive. We previously reported 42% (5/12) of sterile protection in malaria-unexposed, Duffy-positive (Fy+) volunteers immunized with PvRAS followed by a controlled human malaria infection (CHMI). Using a custom protein microarray displaying 515 Pv antigens, we found that PvRAS group seroreactivity was lower in protected than non-protected volunteers. Nevertheless, protected volunteers showed higher reactivity to PvCSP and other antigens. In Fy- volunteers immunized with non-irradiated Pv-infected mosquitoes, parasite reactivity increased throughout immunizations. Mock-vaccinated Fy + volunteers developed a vigorous response to CHMI. These findings allowed the identification of novel parasite antigens currently being pursued as vaccine candidates.