Neutralizing monoclonal antibodies block human immunodeficiency virus type 1 infection of dendritic cells and transmission to T cells

Sarah S. Frankel, Ralph M. Steinman, Nelson L. Michael, Silvia Ratto Kim, Nina Bhardwaj, Melissa Pope, Mark K. Louder, Philip K. Ehrenberg, Paul W.H.I. Parren, Dennis R. Burton, Hermann Katinger, Thomas C. Vancott, Merlin L. Robb, Deborah L. Birx, John R. Mascola

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Prevention of the initial infection of mucosal dendritic cells (DC) and interruption of the subsequent transmission of HIV-1 from DC to T cells are likely to be important attributes of an effective human immunodeficiency virus type 1 (HIV-1) vaccine. While anti-HIV-1 neutralizing antibodies have been difficult to elicit by immunization, there are several human monoclonal antibodies (MAbs) that effectively neutralize virus infection of activated T cells. We investigated the ability of three well-characterized neutralizing MAbs (IgG1b12, 2F5, and 2G12) to block HIV-1 infection of human DC. DC were generated from CD14+ blood cells or obtained from cadaveric human skin. The MAbs prevented viral entry into purified DC and the ensuing productive infection in DC/T-cell cultures. When DC were first pulsed with HIV-1, MAbs blocked the subsequent transmission to unstimulated CD3+ T cells. Thus, neutralizing antibodies can block HIV-1 infection of DC and the cell-to-cell transmission of virus from infected DC to T cells. These data suggest that neutralizing antibodies could interrupt the initial events associated with mucosal transmission and regional spread of HIV-1.

Original languageEnglish
Pages (from-to)9788-9794
Number of pages7
JournalJournal of Virology
Volume72
Issue number12
DOIs
StatePublished - Dec 1998
Externally publishedYes

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