Nature：基于T细胞的HIV-1疫苗开发策略仍有可行性

专题： Nature报道
最近遭受的挫折促使人们对 艾滋病疫苗 领域进行一次重大的重新评估。人们一直问的一个问题是，是否继续基于T-细胞的HIV-1疫苗的开发。现在，用一种新疫苗在患有“猴免疫缺陷综合症”（SIV）的猴子身上所进行的一项研究表明，基于T-细胞的策略仍然是有潜在可行性的。该疫苗利用两种表达SIV Gag蛋白的腺病毒 载体 (rAd26 prime/rAd5 boost)制成。它能诱发强效T-细胞免疫反应，并使猴子在病毒感染方面受到一定保护。这些发现为用于防治HIV-1的新一代基于T-细胞的疫苗候选药物的设计提供了线索。（ 生物谷 Bioon.com）
生物谷 推荐原始出处：
Nature 457, 87-91 (1 January 2009) doi:10.1038/nature07469
Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys
Jinyan Liu1, Kara L. O'Brien1, Diana M. Lynch1, Nathaniel L. Simmons1, Annalena La Porte1, Ambryice M. Riggs1, Peter Abbink1, Rory T. Coffey1, Lauren E. Grandpre1, Michael S. Seaman1, Gary Landucci2, Donald N. Forthal2, David C. Montefiori3, Angela Carville4, Keith G. Mansfield4, Menzo J. Havenga5, Maria G. Pau6, Jaap Goudsmit6 & Dan H. Barouch1
1 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA2 University of California, Irvine School of Medicine, Irvine, California 92697, USA3 Duke University Medical Center, Durham, North Carolina 27710, USA4 New England Primate Research Center, Southborough, Massachusetts 01772, USA5 TNO Biosciences, 2301 CE, Leiden, The Netherlands6 Crucell Holland BV, 2301 CA, Leiden, The Netherlands
A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans1, 2. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIVMAC251 challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1.