Assessment of different sources of variation in the antibody responses to specific malaria antigens in children in Papua New Guinea

Background A potential problem for malaria vaccine development and testing is between-host variation in antibody responses to specific malaria antigen s. Previous work in adults in an area highly endemic for Plasmodium falcipa rum in Papua New Guinea found that genetic regulation partly explained hete rogeneity in responsiveness. We have now assessed the relative contribution s of environmental and genetic factors in total IgG responses to specific m alaria antigens in children, and quantified temporal variation within indiv iduals of total IgG responses. Methods Total IgG responses against schizont extract, merozoite surface pro tein-1, merozoite surface protein-2, ring-infected erythrocyte surface anti gen, and SPf66 were measured by ELISA. Variance component analysis was used to estimate the variation explained by genetic and environmental factors i n these antibody responses. Intra- and inter-class correlations of antibody responses within relative pairs were estimated. We adjusted for age, P. fa lciparum density, sex and village differences either within or prior to the analysis. Results For all malaria antigens, temporal variation in the total IgG respo nse was the predominant source of variation. There was substantial familial aggregation of all IgG responses, but it remained unclear how much this cl ustering was attributable to genetic factors and how much to a common envir onment in the household. The remaining variance, which could not be explain ed by either of the above, was very small for most of the antigens. Conclusions Temporal variation and clustering of immune responses to specif ic malaria antigens need to be taken into account when planning, conducting and interpreting immuno-epidemiological and vaccine studies.