Improved Pregnancy Outcomes In Women Exposed To Malaria With High Antibody Levels Against Plasmodium Falciparum

Background. Antibodies against VAR2CSA, the Plasmodium falciparum variant surface antigen that binds placental chondroitin sulfate A, have been suggested to mediate protection against malaria in pregnancy but also to be markers of infection. Here, we aimed to identify clinically relevant antibody responses, taking into consideration variations in parasite exposure and human immunodeficiency virus type 1 (HIV) infection status.Methods. Levels of immunoglobulin G (IgG) against placental and pediatric isolates, VAR2CSA (DBL2X, DBL3X, DBL5 epsilon, and DBL6 epsilon domains), and other blood-stage antigens (DBL gamma, DBL alpha, MSP1(19), AMA1, and EBA175) were measured in plasma specimens from 293 pregnant Mozambican women at delivery. Associations between antibody responses, factors influencing malaria exposure, HIV infection status, and pregnancy outcomes were assessed.Results. Maternal antibodies were affected by placental infection, parity, season, and neighborhood of residence. HIV infection modified these associations and attenuated the parity-dependent increase in IgG level. High levels of antibody against AMA1, DBL3X, DBL6 epsilon, placental isolates, and pediatric isolates were associated with increased weight and gestational age of newborns (P < .036) among women with malaria episodes during pregnancy.Conclusions. Antiparasite IgGs in women at delivery are affected by HIV infection, as well as by variations in the exposure to P. falciparum. Heterogeneity of malaria transmission needs to be considered to identify IgGs against VAR2CSA and other parasite antigens associated with improved pregnancy outcomes.