The magnitude of antibody responses varies across the individual
proteins that constitute any given microorganism, both in the context of natural
infection and vaccination with attenuated or inactivated pathogens. The
protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal
malaria, we examined the relationship between
immunoglobulin G (
IgG) responses to 861 Plasmodium falciparum
proteins and specific features of these
proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that
IgG reactivity was significantly higher to extracellular and plasma membrane
proteins and also correlated positively with both
protein abundance and degree of
protein polymorphism. Conversely,
IgG reactivity was significantly lower to
proteins predicted to have human orthologs. These findings provide insight into
protein-specific factors that are associated with variability in the magnitude of antibody responses to natural P. falciparum
infection-data that could inform
vaccine strategies to optimize antibody-mediated immunity as well as the selection of
antigens for sero-diagnostic purposes.