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Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies

Abstract

The development of the human immunodeficiency virus-1 (HIV-1)/simian immunodeficiency virus (SIV) chimeric virus macaque model (SHIV) permits the in vivo evaluation of anti-HIV-1 envelope glycoprotein immune responses1,2,3. Using this model, others, and we have shown that passively infused antibody can protect against an intravenous challenge4,5. However, HIV-1 is most often transmitted across mucosal surfaces6,7,8,9 and the intravenous challenge model may not accurately predict the role of antibody in protection against mucosal exposure. After controlling the macaque estrous cycle with progesterone10, anti-HIV-1 neutralizing monoclonal antibodies 2F5 and 2G12, and HIV immune globulin were tested11,12,13. Whereas all five control monkeys displayed high plasma viremia and rapid CD4 cell decline, 14 antibody-treated macaques were either completely protected against infection or against pathogenic manifestations of SHIV-infection. Infusion of all three antibodies together provided the greatest amount of protection, but a single monoclonal antibody, with modest virus neutralizing activity, was also protective. Compared with our previous intravenous challenge study with the same virus and antibodies5, the data indicated that greater protection was achieved after vaginal challenge. This study demonstrates that antibodies can affect transmission and subsequent disease course after vaginal SHIV-challenge; the data begin to define the type of antibody response that could play a role in protection against mucosal transmission of HIV-1.

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Figure 1: Plasma SHIV RNA (a) and peripheral CD4% (b) for four groups of monkeys after antibody infusion and vaginal SHIV89.6PD challenge.

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Acknowledgements

We thank Chris Sapan for supplying the HIVIG, Norman Letvin, Keith Reimann, and Yichen Lu for the SHIV89.6PD, Robin Garner for statistical advice, Dawn Harris for veterinary care and Francine McCutchan and Nelson Michael for manuscript reviews. We appreciate the excellent technical assistance from Mark Louder, Marcin Iwanicki, Jack Greenhouse, Mike Eller, and Jake Yalley-Ogunro. This work was supported in part by grants from the National Heart Lung and Blood Institute and by Cooperative Agreement between the U.S. Army Medical Research and Materiel Command and the Henry M. Jackson Foundation for the Advancement of Military Medicine.United States Department of Defense Disclaimer: The views and opinions expressed herein are those of the authors and do not purport to reflect the official policy or position of the U.S. Army, U.S. Navy or the Department of Defense.

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Correspondence to John R. Mascola.

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Mascola, J., Stiegler, G., VanCott, T. et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 6, 207–210 (2000). https://doi.org/10.1038/72318

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