VAR2CSA-reactive IgG in Brazilian women exposed to Plasmodium falciparum or P. vivax infection during pregnancy
Year: 2025
Type: article
Study design: Observational Study
Abstract: ABSTRACT Placental malaria (PM) causes mortality and severe morbidity in areas with stable Plasmodium falciparum transmission. The selective placental accumulation of P. falciparum -infected erythrocytes (IEs) is mediated by VAR2CSA, a PfEMP1-type parasite ligand that binds exclusively to placenta-restricted CSA. VAR2CSA-specific IgG is therefore generally restricted to women exposed to P. falciparum infection during pregnancy. However, widespread acquisition of VAR2CSA-reactive IgG outside pregnancy among Colombian and Brazilian individuals has been reported, supposedly due to cross-reactivity between VAR2CSA and the P. vivax -specific antigen PvDBP. Here, we measured levels and Fc-afucosylation of VAR2CSA-reactive IgG in plasma from pregnant Brazilian women at delivery, using full-length VAR2CSA (FV2) expressed in baculovirus-transfected insect cells (FV2 BIC ) or Chinese hamster ovary cells (FV2 CHO ) as well as the corresponding native antigen (IT4VAR04) on the IE surface. We also measured levels of IgG specific for GLURP ( P. falciparum- specific) and PvDBP ( P. vivax -specific). FV2 CHO -specific IgG levels were lower than FV2 BIC -reactive IgG levels. Furthermore, only FV2 CHO -specific IgG was restricted to women exposed to P. falciparum during pregnancy. Levels of PvDBP-specific IgG were significantly higher among P. vivax -exposed pregnant women but did not correlate with FV2-specific IgG levels. Finally, FV2 CHO -specific IgG was markedly Fc-afucosylated in contrast to FV2 BIC -reactive IgG. Our findings caution against using levels of IgG reacting with recombinant proteins expressed in insect cells as a measure of exposure to VAR2CSA during pregnancy, at least in South America. Furthermore, our data do not support the hypothesis that exposure to PvDBP induces IgG that cross-reacts with VAR2CSA and contributes to protection against PM.
Source: Infection and Immunity
DOI: 10.1128/iai.00516-25
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415736117