JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01809-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Isolation of human monoclonal antibodies that potently neutralize HCMV infection by targeting different epitopes on the gH/gL/UL128-131A complex

Annalisa Macagno^*, Nadia Bernasconi, Fabrizia Vanzetta, Erica Dander, Antonella Sarasini, Maria Grazia Revello, Giuseppe Gerna, Federica Sallusto, and Antonio Lanzavecchia^*

Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland; Servizio di Virologia, Fondazione IRCCS Policlinico San Matteo, I-27100 Pavia, Italy

^* To whom correspondence should be addressed. Email: annalisa.macagno{at}irb.unisi.ch. lanzavecchia{at}irb.unisi.ch.

Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immunocompromised patients and infected foetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (IC₉₀ values ranging from 5 to 200 pM) HCMV infection of endothelial, epithelial and myeloid cells. With a 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 immunotherapy 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.