Plasmodium PIMMS43 is required for ookinete evasion of the mosquito complement-like response and sporogonic development in the oocyst

Malaria transmission requires parasites to successfully infect a female mosquito, surviving a series of robust innate immune responses. Understanding how parasites evade these responses can highlight new ways to block malaria transmission. We show that ookinete and sporozoite surface protein PIMMS43 is required for ookinete evasion of the complement-like system and for sporogonic development in the oocyst. Disruption of PIMMS43 triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing the complement-like system restores ookinete-to-oocyst transition. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African populations indicates allelic adaptation to sympatric vector populations. These data significantly add to our understanding of mosquito-parasite interactions and identify PIMMS43 as a target of interventions aiming at malaria transmission blocking.