Neutralizing antibodies are unable to inhibit direct viral cell-to-cell spread of human cytomegalovirus

- CMV antibodies neutralize virus entry into fibroblasts and epithelial cells.
- CMV neutralizing antibodies do not inhibit viral cell-to-cell spread in plaque reduction assay.
- Antibodies are functional in agarose overlay.
- Ab could not inhibit plaque formation even when cells were not confluent.

Infection with human cytomegalovirus (CMV) during pregnancy is the most common cause of congenital disorders, and can lead to severe life-long disabilities with associated high cost of care. Since there is no vaccine or effective treatment, current efforts are focused on identifying potent neutralizing antibodies. A panel of CMV monoclonal antibodies identified from patent applications, was synthesized and expressed in order to reproduce data from the literature showing that anti-glycoprotein B antibodies neutralized virus entry into all cell types and that anti-pentameric complex antibodies are highly potent in preventing virus entry into epithelial cells. It had not been established whether antibodies could prevent subsequent rounds of infection that are mediated primarily by direct cell-to-cell transmission. A thorough validation of a plaque reduction assay to monitor cell-to-cell spread led to the conclusion that neutralizing antibodies do not significantly inhibit plaque formation or reduce plaque size when they are added post-infection.