HIV-1 Vaccine Trials: Evolving Concepts and Designs.
HIV-1 Vaccine Trials: Evolving Concepts and Designs.
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DOI：
10.2174/1874613601206010274
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Yamamoto JK
中科院分区：
文献类型：
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作者：
Sanou MP;De Groot AS;Murphey-Corb M;Levy JA;Yamamoto JK
根除艾滋病毒/艾滋病大流行需要一种有效的预防性艾滋病毒-1疫苗，但设计这种疫苗是一项挑战。尽管在产生体液和细胞免疫反应的疫苗技术和方法方面取得了许多进展，但针对艾滋病毒/艾滋病的主要第二和第三阶段疫苗试验只取得了适度的成功。RV144 iii期临床试验在泰国取得的温和成果再次强调了产生强大的抗HIV体液和细胞反应的重要性。虽然一些团体正在寻求以抗体为导向的方法，但另一些团体正试图开发针对细胞介导免疫的疫苗，因为有证据表明ctl对控制艾滋病毒复制很重要。i期和-IIa期多表位疫苗试验已经进行，疫苗免疫原由已知的在HIV亚型中保守的CTL表位组成，但到目前为止还不能诱导强大和一致的抗HIV CTL反应。本文综述了基于t细胞表位的疫苗开发的概念、相关临床疫苗试验的结果以及增强细胞介导方法的免疫原性的努力。此外，我们描述了一种基于鉴定含有保守的HIV特异性t细胞表位的SIV和FIV抗原的新方法，代表了开发针对全球HIV分离株的有效HIV疫苗的替代方法。
An effective prophylactic HIV-1 vaccine is needed to eradicate the HIV/AIDS pandemic but designing such a vaccine is a challenge. Despite many advances in vaccine technology and approaches to generate both humoral and cellular immune responses, major phase-II and -III vaccine trials against HIV/AIDS have resulted in only moderate successes. The modest achievement of the phase-III RV144 prime-boost trial in Thailand re-emphasized the importance of generating robust humoral and cellular responses against HIV. While antibody-directed approaches are being pursued by some groups, others are attempting to develop vaccines targeting cell-mediated immunity, since evidence show CTLs to be important for the control of HIV replication. Phase-I and -IIa multi-epitope vaccine trials have already been conducted with vaccine immunogens consisting of known CTL epitopes conserved across HIV subtypes, but have so far fallen short of inducing robust and consistent anti-HIV CTL responses. The concepts leading to the development of T-cell epitope-based vaccines, the outcomes of related clinical vaccine trials and efforts to enhance the immunogenicity of cell-mediated approaches are summarized in this review. Moreover, we describe a novel approach based on the identification of SIV and FIV antigens which contain conserved HIV-specific T-cell epitopes and represent an alternative method for developing an effective HIV vaccine against global HIV isolates.