Antibody levels to recombinant VAR2CSA domains vary with Plasmodium falciparum parasitaemia, gestational age, and gravidity, but do not predict pregnancy outcomes

Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodiesto the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibodylevels and thereby confound analyses of immune protection, gravidity-dependent changes in antibodylevels during and after infection, and the effect of VAR2CSA antibodieson pregnancy outcomes were evaluated. Pregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30–32, and delivery. Antibodylevels to VAR2CSA domains were measured using a multiplex bead-based assay. Antibodylevels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibodylevels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodieslevels sharply declined after an infection. A relationship between any VAR2CSA antibodyspecificity and protection from adverse pregnancy outcomes was not detected. During malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibodyreactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.