Antibody responses against P. falciparum MSP2

Antibody responses against the blood-stage antigen merozoite surface protein 2 (MSP2) are associated with protection from P. falciparum malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. We performed high fidelity, long-read sequencing and expressed four msp2 variants from parasite isolates in order to investigate naturally acquired antibody responses towards different variants, in highly exposed individuals and in non-immune travelers. IgG responses against recombinantly expressed full-length, central polymorphic regions, and peptides derived from the conserved termini of MSP2 variants sequenced from patient isolates, were tested in plasma from travelers with recent, acute malaria and from individuals living in an endemic area of Tanzania. IgG responses towards full MSP2 and truncated MSP2 antigens were MSP2-variant specific. IgG from individuals living in an endemic region, many who were asymptomatically infected, did not recognize the conserved termini by ELISA. Our results suggest that responses to the variable regions are important for the development of naturally acquired immunity towards MSP2.