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

Ann J. Hessell, Lars Hangartner, Meredith Hunter, Carin E.G. Havenith, Frank J. Beurskens, Joost M. Bakker, Caroline M.S. Lanigan, Gary Landucci, Donald N. Forthal, Paul W.H.I. Parren, Preston A. Marx, Dennis R. Burton

    Research output: Contribution to journalArticle

    615 Scopus citations

    Abstract

    Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine. 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. 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.

    Original languageEnglish (US)
    Pages (from-to)101-104
    Number of pages4
    JournalNature
    Volume449
    Issue number7158
    DOIs
    StatePublished - Sep 6 2007

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'Fc receptor but not complement binding is important in antibody protection against HIV'. Together they form a unique fingerprint.

  • Cite this

    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. https://doi.org/10.1038/nature06106