Variant-specific antibodies to merozoite surface protein 2 and clinical expression of Plasmodium falciparum malaria in rural Amazonians

Abstract

Naturally acquired antibodies to five variants of the merozoite surface protein 2 (MSP-2), a target of clinical immunity to Plasmodium falciparum malaria, were measured in a cohort of rural Amazonians. Local MSP-2 variants comprised both highly divergent families of alleles (FC27 and 3D7). Total IgG antibodies to two FC27-type antigens were found in 22-28% of subjects at baseline, with substantial cross-reactivity between variants and stable concentrations and specificities over time. The IgG antibodies to three 3D7-type antigens were less prevalent (6-7%), less cross-reactive, and short-lived; subsequent exposure to 3D7-type parasites rarely elicited homologous response. The clinical spectrum of 109 incident P. falciparum infections in our cohort ranged between asymptomatic infection and fully symptomatic but uncomplicated disease. Parasitemia at the time of diagnosis, rather than cumulative malaria exposure or acquired immunity (presence of variant-specific antibodies matching the MSP-2 type in infecting parasites), was a major predictor of perceived symptom severity.