Humoral and Cellular Immunity to Plasmodium falciparum Merozoite Surface Protein 1 and Protection From Infection With Blood-Stage Parasites

Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts. Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon gamma (IFN-gamma) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re) infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya. Results. Positive IFN-gamma enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP1(42) 3D7 were associated with delayed time to (re) infection, whereas high-titer IgG antibodies to MSP1(42) 3D7 or FVO alleles were not independently predictive of the risk of (re) infection. When IFN-gamma and IL-10 responses were both present, the protective effect of IFN-gamma was abrogated. A Cox proportional hazard model including IFN-gamma, IL-10, MSP1(42) 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-gamma responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia. Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.