Nature：艾滋病疫苗治疗新进展
生物谷援引德国《商报》9月6日报道，探求对付艾滋病病原体———HI病毒———的疫苗的工作很快就会取得新的进展。根据美国拉霍亚斯克里普斯研究所的安·赫塞尔牵头的研究小组的探讨，迄今为止试验的疫苗缺乏一种起决定作用的特性。
他们在今天出版的一期《自然》周刊上解释说，这样一种疫苗不仅应该阻止病毒细胞侵入健康的细胞，而且也应该激活人体的其他防御机制。
HI病毒使部分免疫系统不起作用，以至于人体不再能抵御其他病原体。在正常的免疫系统中，人体在接触病原体时会产生合适的抗体。这种抗体与病毒壳的抗原结合，从而阻止病毒侵入和感染人体细胞。
据安·赫塞尔说，使用的艾滋病疫苗的抗体不仅应该与在体内自由环流的病毒直接对接，而且也应该在本体的防御细胞中占有专门的受体。这种所谓的Fc段受体处于免疫防御的杀手细胞和吞噬细胞的表面。只有当疫苗的抗体通过Fc段受体也与这种免疫细胞对接时，免疫细胞才能识别和消灭体内已经感染的细胞。
这是研究人员从猴子身上试验和人造HI病毒中得出的结论。他们去除了疫苗中的抗体Fc段结合点。猴子体内的免疫细胞迅速失去有效杀灭病毒的能力。
但马里兰疫苗研究中心的约翰·马斯科拉在同时发表的一篇评论中警告说，人们不能对通过Fc段受体的防御机理估计过高。他说，过去仅仅寄希望于这种方法的试验很少取得效果，或者根本没有取得效果。（新华网）
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.
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