Congenital human cytomegalovirus (HCMV)
infection is a leading cause of
birth defects worldwide, yet the most effective strategies for preventing virus transmission during pregnancy are unknown. We measured the efficacy of human
monoclonal antibodies (mAbs) to HCMV attachment/entry factors
glycoprotein B (gB) and the pentameric complex, gH/gL-pUL128-131, in preventing
infection and spread of a clinical strain in primary placental cells and explants of developing anchoring villi. A total of 109 explants from five first-trimester placentas were cultured, and
infection was analyzed in over 400 cell columns containing ~120,000 cytotrophoblasts (CTBs). mAbs to gB and gH/gL, 3-25 and 3-16, respectively, neutralized
infection in stromal fibroblasts and trophoblast progenitor cells. mAbs to pUL128-131 of the pentameric complex, 1-103 and 2-18, neutralized
infection of amniotic epithelial cells better than mAbs 3-25 and 3-16 and hyperimmune
globulin. Select mAbs neutralized
infection of cell column CTBs, with mAb 2-18 most effective, followed by mAb 3-25. Treatment of anchoring villi with mAbs postinfection reduced spread in CTBs and impaired formation of virion assembly compartments, with mAb 2-18 achieving better suppression at lower concentrations. These results predict that
antibodies generated by HCMV
vaccines or used for passive immunization have the potential to reduce transplacental transmission and congenital disease.