Antibodies to Variant Surface Antigens of Plasmodium falciparum-Infected Erythrocytes and Adhesion Inhibitory Antibodies Are Associated with Placental Malaria and Have Overlapping and Distinct Targets

We measured antibodies to chondroitin sulfate A (CSA)-binding and placental Plasmodium falciparum-infected red blood cells (PRBCs) among pregnant women with or without placental malaria. Immunoglobulin G to PRBC surface antigens was rare in uninfected primigravidae (3.7%), more prevalent in infected primigravidae (70%; P< .001), and common in infected (77%) and uninfected (83%) multigravidae. Similar patterns were seen for agglutinating antibodies, and antibodies were similar among women with past or active placental infection. PRBC adhesion to CSA was inhibited 60% by cells obtained from infected primigravidae but 24% by cells obtained from uninfected primigravidae (P = .025), whereas infection did not alter adhesion inhibition by multigravidae (77% inhibition). There was substantial heterogeneity in antibody type and levels. Antibodies did not correlate with parasite density or pregnancy outcome. Comparisons between antibodies suggest that adhesion-inhibitory antibodies and those to PRBC variant antigens have distinct and overlapping epitopes, may be acquired independently, and have different roles in immunity.