VAR2CSA Antibodies in Non-Pregnant Populations

The Plasmodium falciparum protein VAR2CSA is a critical mediator of placental malaria, and VAR2CSA antibodies (IgGs) are important to protect pregnant women. Although infrequently detected outside pregnancy, VAR2CSA IgGs were reported in men and children from Colombia and Brazil and in select African populations. These findings raise questions about the specificity of VAR2CSA IgGs and the mechanisms by which they are acquired outside pregnancy. Here we review the data on VAR2CSA IgGs in men and children from different malaria-endemic regions. We discuss experimental factors that may affect interpretation of the serological data and consider the biological relevance of VAR2CSA IgGs in non-pregnant populations. We propose potential mechanisms for the acquisition of VARCSA IgGs outside of pregnancy. We identify knowledge gaps and research priorities.