生物谷援引德國《商報》9月6日報道,，探求對付艾滋病病原體———HI病毒———的疫苗的工作很快就會取得新的進展,。根據(jù)美國拉霍亞斯克里普斯研究所的安·赫塞爾牽頭的研究小組的探討,，迄今為止試驗的疫苗缺乏一種起決定作用的特性,。
他們在今天出版的一期《自然》周刊上解釋說,，這樣一種疫苗不僅應該阻止病毒細胞侵入健康的細胞,，而且也應該激活人體的其他防御機制,。
HI病毒使部分免疫系統(tǒng)不起作用,，以至于人體不再能抵御其他病原體。在正常的免疫系統(tǒng)中,，人體在接觸病原體時會產生合適的抗體,。這種抗體與病毒殼的抗原結合，從而阻止病毒侵入和感染人體細胞,。
據(jù)安·赫塞爾說,，使用的艾滋病疫苗的抗體不僅應該與在體內自由環(huán)流的病毒直接對接，而且也應該在本體的防御細胞中占有專門的受體,。這種所謂的Fc段受體處于免疫防御的殺手細胞和吞噬細胞的表面,。只有當疫苗的抗體通過Fc段受體也與這種免疫細胞對接時，免疫細胞才能識別和消滅體內已經感染的細胞,。
這是研究人員從猴子身上試驗和人造HI病毒中得出的結論,。他們去除了疫苗中的抗體Fc段結合點。猴子體內的免疫細胞迅速失去有效殺滅病毒的能力,。
但馬里蘭疫苗研究中心的約翰·馬斯科拉在同時發(fā)表的一篇評論中警告說,，人們不能對通過Fc段受體的防御機理估計過高。他說,，過去僅僅寄希望于這種方法的試驗很少取得效果,，或者根本沒有取得效果。（新華網）
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.
