The Development, Fine Specificity, and Importance of High-Avidity Antibodies to VAR2CSA in Pregnant Cameroonian Women Living in Yaoundé, an Urban City

Pregnant women infected with often produce antibodies ( ) to VAR2CSA, a ligand that binds to placental chondroitin sulfate A causing placental malaria ( ). Antibodies to VAR2CSA are associated with improved pregnancy outcomes. Antibody avidity is a surrogate marker for the extent of maturation of the humoral immune response. Little is known about high avidity Abs to VAR2CSA for women living in urban African cities. Therefore, this study sought to determine: i) if high avidity Abs to full-length VAR2CSA ( ) increase with gravidity in women in Yaoundé, Cameroon exposed to ~ 0.3-1.1 infectious mosquito bites per month, ii) if high avidity Abs to FV2 are directed against a specific region of VAR2CSA, and iii) if having high avidity Abs to FV2 improve pregnancy outcomes. Plasma samples collected at delivery from 695 women who had Abs to FV2 were evaluated. Ab levels and the Avidity Index ( ), defined as the percent Abs remaining bound to FV2 after incubation with 3M NH SCN, were determined. Similar Ab levels to FV2 were present in women of all gravidities (G1 through 6+; =0.80), except significantly lower levels were detected in PM-negative (PM-) primigravidae ( 0.001). Median Ab avidities increased between gravidity 1 and 2 (