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Journal of Virology, December 1998, p. 9788-9794, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells

Sarah S. Frankel,1,2,* Ralph M. Steinman,3 Nelson L. Michael,1 Silvia Ratto Kim,1 Nina Bhardwaj,3 Melissa Pope,3 Mark K. Louder,1 Philip K. Ehrenberg,1 Paul W. H. I. Parren,4 Dennis R. Burton,4 Hermann Katinger,5 Thomas C. VanCott,1 Merlin L. Robb,1 Deborah L. Birx,1 and John R. Mascola1,6

Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville,1 and Department of Infectious Diseases, Naval Medical Research Institute, Bethesda,6 Maryland; Division of AIDS and Emerging Infectious Diseases, Department of Infectious and Parasitic Disease Pathology, Armed Forces Institute of Pathology/American Registry of Pathology, Washington, D.C.2; Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York3; Department of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California4; and University of Agriculture, Institute of Applied Microbiology, Vienna, Austria5

Received 7 July 1998/Accepted 20 August 1998

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.

* Corresponding author. Mailing address: Walter Reed Army Institute of Research, 13 Taft Court, Suite 200, Rockville, MD 20850. Phone: (301) 217-9410. Fax: (301) 762-4177. E-mail: sfrankel{at}hiv.hjf.org.

Journal of Virology, December 1998, p. 9788-9794, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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