Individuals in Plasmodium falciparum endemic areas develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses against P. falciparum is presently limited, particularly among young children. We examined antibodies (IgM, IgG and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children aged 1-4yrs in a malaria endemic region of Papua New Guinea. IgG, IgG1 and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force-of-infection by P. falciparum, accounted for much of the increased risk, suggesting antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and a longitudinal cohort of older children suggests that the lack of protective association was explained by lower antibody levels among young children, and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure, and that with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity.
Link to publisher’s web site