生物谷报道：很多有效疫苗通过诱导中和抗体来发挥作用，这种方法是HIV疫苗的一个研究重点。但一项新的研究表明，抗HIV抗体在以两种方式发挥作用时最有效：一种是通过中和，即直接杀死病毒，阻止其进入T-细胞；另一种是通过杀死感染的细胞。研究人员将保护人体不受HIV感染的一种具有中和作用的人体抗体的基因工程版本用于一个猴子模型，发现保护作用不仅依赖于该抗体的中和活性，而且依赖于其与促动细胞（effector cells）上的Fc受体的相互作用，该受体的作用可能是降低被感染细胞所产生的病毒数量。这项工作说明，用能够同时利用具有中和作用的抗体和通过巨噬细胞及细胞分裂素等实现的由细胞调控的免疫力的疫苗，也许能够获得最好的结果。
原始出处:
Nature 449, 101-104 (6 September 2007) | doi:10.1038/nature06106; Received 27 April 2007; Accepted 20 July 2007
Fc receptor but not complement binding is important in antibody protection against HIV
Ann J. Hessell1,5, Lars Hangartner1,5, Meredith Hunter2, Carin E. G. Havenith3, Frank J. Beurskens3, Joost M. Bakker3, Caroline M. S. Lanigan1, Gary Landucci4, Donald N. Forthal4, Paul W. H. I. Parren3, Preston A. Marx2 & Dennis R. Burton1
Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Tulane National Primate Research Center, Tulane University, Covington, Louisiana 70433, USA
Genmab, 3584 CM Utrecht, The Netherlands
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, California 92697, USA
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).
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.
