NIH Research Festival
FARE Award Winner
It is well known that the magnitude of pathogen-specific IgG responses during natural infections varies across individual antigens, yet the factors underlying this heterogeneity are unclear. In a study of 267 individuals exposed to intense seasonal malaria transmission, we examined the relationship between the magnitude of IgG responses to 1087 Plasmodium falciparum antigens and several features of these antigens including their subcellular location, relative abundance, molecular weight, whether or not they contain predicted MHC class II epitopes, their 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 highly abundant proteins and highly polymorphic proteins; whereas IgG reactivity was significantly lower to proteins with human orthologs. Multiple regression analysis revealed that extracellular location independently predicted higher IgG reactivity, whereas location in the plasma membrane predicted low IgG reactivity in highly conserved membranes, and conversely high reactivity in highly polymorphic membranes. We observed the same findings in our cohort the following malaria season. These results provide insights into the proteomic features of antigens that underlie the variation in antibody responses during a natural infection, information that could inform vaccine strategies.
Scientific Focus Area: Microbiology and Infectious Diseases
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