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Fc receptor but not complement binding is important in antibody protection against HIV


Hessell, A J; Hangartner, L; Hunter, M; Havenith, C E G; Beurskens, F J; Bakker, J M; Lanigan, C M S; Landucci, G; Forthal, D N; Parren, P W H I; Marx, P A; Burton, D R (2007). Fc receptor but not complement binding is important in antibody protection against HIV. Nature, 449(7158):101-104.

Abstract

Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine1,2.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 challenge3,4. 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.

Abstract

Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine1,2.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 challenge3,4. 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:6 September 2007
Deposited On:29 Apr 2015 13:55
Last Modified:05 Apr 2016 19:14
Publisher:Nature Publishing Group
ISSN:0028-0836
Funders:NIH grant (D.R.B.), Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative, Swiss National Foundation Fellowship (L.H.), NIH grant (D.N.F.)
Publisher DOI:https://doi.org/10.1038
Related URLs:http://www.nature.com/nature/journal/v449/n7158/full/nature06106.html
http://www.nature.com
PubMed ID:17805298

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