生物谷報(bào)道：很多有效疫苗通過誘導(dǎo)中和抗體來發(fā)揮作用,，這種方法是HIV疫苗的一個(gè)研究重點(diǎn),。但一項(xiàng)新的研究表明,，抗HIV抗體在以兩種方式發(fā)揮作用時(shí)最有效：一種是通過中和，即直接殺死病毒,，阻止其進(jìn)入T-細(xì)胞,；另一種是通過殺死感染的細(xì)胞,。研究人員將保護(hù)人體不受HIV感染的一種具有中和作用的人體抗體的基因工程版本用于一個(gè)猴子模型，發(fā)現(xiàn)保護(hù)作用不僅依賴于該抗體的中和活性,，而且依賴于其與促動細(xì)胞（effector cells）上的Fc受體的相互作用,，該受體的作用可能是降低被感染細(xì)胞所產(chǎn)生的病毒數(shù)量。這項(xiàng)工作說明,，用能夠同時(shí)利用具有中和作用的抗體和通過巨噬細(xì)胞及細(xì)胞分裂素等實(shí)現(xiàn)的由細(xì)胞調(diào)控的免疫力的疫苗,，也許能夠獲得最好的結(jié)果。
原始出處:
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: [email protected]).
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.
