Isolation of Human Monoclonal Antibodies That Potently Neutralize

Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immuno-compromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC90] values ranging from 5 to 200 pM) HCMV infection of endothelial, epithelial, and myeloid cells. With the single exception of an antibody that bound to a conserved epitope in the UL128 gene product, all other antibodies bound to conformational epitopes that required expression of two or more proteins of the gH/gL/UL128-131A complex. Antibodies against gB, gH, or gM/gN were also isolated and, albeit less potent, were able to neutralize infection of both endothelial-epithelial cells and fibroblasts. This study describes unusually potent neutralizing antibodies against HCMV that might be used for passive immuno-therapy and identifies, through the use of such antibodies, novel antigenic targets in HCMV for the design of immunogens capable of eliciting previously unknown neutralizing antibody responses. Human cytomegalovirus (HCMV) is a member of the her-pesvirus family which is widely distributed in the human pop-ulation and can cause severe disease in immunocompromised patients and upon infection of the fetus. HCMV infectio