IGG3 ANTIBODIES TO PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-2 (MSP2) - INCREASING PREVALENCE WITH AGE AND ASSOCIATION WITH CLINICAL IMMUNITY TO MALARIA

In a cross-sectional survey carried out in west Africa (The Gambia), w here Plasmodium falciparum malaria is endemic with seasonal transmissi on, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP 2 was determined by ELISA. The IgG-subclass profile of IgG-positive se ra was assessed. Antibody prevalence was age-dependent, reaching a pea k during adolescence. In MSP2-seropositive individuals, there was a pr edominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies w ere prevalent in children less than 10 years of age, whereas in adoles cents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transm ission season were tested for the presence of anti-MSP2 antibodies. Th e subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of differen t IgG subclasses and resistance to clinical malaria was tested. The pr esence of IgG3 antibodies to MSP2 serogroup A was negatively associate d with the risk of clinical malaria whereas IgG1 antibodies to MSP2 se rogroup B were associated with an increased risk of clinical infection . Our data suggest that age/exposure-related acquisition of IgG3 antib odies to MSP2, may contribute to the development of clinically protect ive immunity to malaria.