Anti-VAR2CSA antibodies (IgGs) are significantly more common in men and children in South America than in Africa.
IgGs to VAR2SCA are common in men and children where both Plasmodium falciparum and Plasmodium vivax are prevalent and are not common where coinfection does not occur.
Factors influencing the detection of VAR2CSA IgGs – including the type of construct of the VAR2CSA antigen, recombinant versus native protein, choice of protein expression system, choice of negative controls, infection status of the participant, and different data analysis methods – can impact seropositivity across studies.
Reactivity to VAR2CSA antigen exclusively may not fully describe the characteristics of anti-VAR2CSA IgGs and suggests the relevance of evaluating the functional activity of these IgGs.
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.
