Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria infection would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.

Methods. The relationship between IgG antibody and IFN-gamma and IL-10 responses to the 42 kD C-terminal fragment of Plasmodium falciparum Merozoite Surface Protein 1 (MSP142) and risk-of-(re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in a holoendemic area of western Kenya.

Results. Positive IFN-gamma ELISA and ELISPOT responses to MSP-142 3D7 were associated with delayed time-to-(re)infection whereas high-titer IgG antibodies to MSP-142 3D7 or FVO alleles were not independently predictive of 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, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age and infection status at baseline, showed time to blood-stage infection correlated positively with IFNgamma+ responses and negatively with IL-10+ responses, younger age, and asymptomatic parasitemia.

Conclusion. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to either measure alone.