Wider antibody breadth against multiple Plasmodium falciparum antigens is associated with reduced risk of malaria in a transmission hotspot in southern Ghana

Objectives: Naturally acquired immunity to malaria results from repeated infection with Plasmodium parasites. However, identifying immune correlates of immunity against febrile malaria is quite challenging. Here we investigated antigenic targets of malaria protective antibodies in populations residing a malaria transmission hotspot in southern Ghana. Method: We enrolled 973 children, aged 6 months to 12 years, in southern Ghana out of which 211 were infected at least once with Plasmodium falciparum in a 50-week longitudinal cohort study. Total IgG levels in baseline plasma samples were determined using indirect ELISA. Results: We found a significant association between higher IgG levels to MSP3 (adjusted P-value [aP] = 0.0002), GLURP-R2 (aP = 0.0026), MSP DBL2 (aP = 0.004) and N-MSP3 (aP = 0.002), and protection from febrile malaria. A negative association between higher antibody levels to MSP3, GMZ2, GLURP-R2 and MSPDBL2 and parasite density was also observed. Wider antibody breadth was associated with protection against febrile malaria and single, compared to multiple malaria episodes. Conclusions: Specific antibody levels and breadth of responses against multiple P. falciparum surface antigens protect against febrile malaria, parasitaemia and multiple malaria episodes. This data supports the development of multivalent vaccines targeting P. falciparum surface antigens in high malaria endemic settings.