Postattachment Neutralization of a Primary Strain of HIV Type 1 in Peripheral Blood Mononuclear Cells Is Mediated by CD4-Specific Antibodies But Not by a Glycoprotein 120-Specific Antibody that Gives Potent Standard Neutralization

Abstract

De novo infecting HIV-1 or virus released from an infected cell in vivo attaches relatively quickly to a target cell, but the rate of fusion-entry of such virus is slow, with 50% entry taking≥2 hr. It is thus desirable that antibodies stimulated by any vaccine or given in immunotherapy are able to neutralize not only free virus, but also virus attached to the target cell. Here we investigated postattachment neutralization (PAN) of a primary HIV-1 strain (JRCSF) in peripheral blood mononuclear cells and of a T cell line-adapted strain (IIIB) in C8166 T lymphoblastoid cells, using the highly potent gp120-specific human monoclonal b12 monoclonal IgG, and monoclonal antibodies specific for the CD4 primary cell receptor. In addition, we improved the experimental protocols of related studies by using a pulse of antibody, thus avoiding the complication of neutralizing progeny virus. We found that b12 IgG PAN was inefficient, with PAN of IIIB needing a 1000-fold greater concentration of antibody than was required for standard neutralization, and PAN of JRCSF being detected erratically only at 4°C and unphysiologically high concentrations (300 μg/ml). Nonetheless, under identical conditions a 10-μg/ml pulse of the CD4-specific MAb Q4120 gave up to 99% PAN of JRCSF, and more than 95% even when added 3 hr after infection at 37°C. Possible mechanisms by which PAN by CD4- specific antibodies is mediated are discussed. We suggest that such anti-CD4 antibodies should be considered as a component of HIV-1 immunotherapy.