1. Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
2. Tulane National Primate Research Center, Tulane University, Covington, Louisiana 70433, USA
3. Genmab, 3584 CM Utrecht, The Netherlands
4. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California 92697, USA
5. These authors contributed equally to this work.

Correspondence to: Dennis R. Burton¹ Correspondence and requests for materials should be addressed to D.R.B. (Email: burton@scripps.edu).

Abstract

Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine^{1, 2}. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge^{3, 4}. However, the mechanism(s) by which neutralizing antibodies afford protection against HIV is not understood and, in particular, the role of antibody Fc-mediated effector functions is unclear. Here we report that there is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody. No loss of antibody protective activity is associated with the elimination of complement binding alone. Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complexed infected cells is important in reducing virus yield from infected cells. Overall, the data suggest the potential importance of activity against both infected cells and free virus for effective protection against HIV.

1. Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
2. Tulane National Primate Research Center, Tulane University, Covington, Louisiana 70433, USA
3. Genmab, 3584 CM Utrecht, The Netherlands
4. Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California 92697, USA
5. These authors contributed equally to this work.

Correspondence to: Dennis R. Burton¹ Correspondence and requests for materials should be addressed to D.R.B. (Email: burton@scripps.edu).

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