Full-length merozoite surface protein 1 of Plasmodium falciparum is a major target of protective immunity following controlled human malaria infections
Rosenkranz, M.; Nkumama, I. N.; Kraker, S.; Blickling, M.; Mwai, K.; Odera, D.; Tuju, J.; Fürle, K.; Frank, R.; Chepsat, E.; Kapulu, M. C.; CHMI-SIKA study team, ; Osier, F. H. A.
Show abstract
The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of the invasive merozoite stages of Plasmodium falciparum and has long been considered a key target of protective immunity. However, previous studies focused on small C-terminal fragments and potentially missed the opportunity to identify important epitopes that are relevant for protection. We used samples from a controlled human malaria challenge (CHMI) study in semi-immune volunteers to show that levels of pre-challenge antibodies directed against the full-length MSP1 (MSP1FL) are significantly correlated with protection from malaria. Furthermore, we showed that anti-MSP1FL antibodies induced five distinct Fc-mediated effector mechanisms: complement fixation, phagocytosis, respiratory burst, degranulation and IFN{gamma} production, each of which was strongly associated with protection. The breadth of Fc-mediated effector functions was the strongest correlate of protection. Our findings suggest that MSP1FL is an important target of functional antibodies that contribute to a protective immune response against malaria and support the development of MSP1FL-based vaccines.
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