HIV-1 vaccine development: tackling virus diversity with a multi-envelope cocktail
HIV-1 vaccine development: tackling virus diversity with a multi-envelope cocktail
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DOI：
10.2741/2706
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Slobod, Karen S.
中科院分区：
文献类型：
--
作者：
Hurwitz, Julia L.;Zhan, Xiaoyan;Slobod, Karen S.
设计全球HIV-1疫苗的一个主要障碍是病毒的多样性。目前，数据表明，包含单一抗原的疫苗将不能产生广泛反应性的B细胞和T细胞应答，这些应答能够赋予针对HIV-1的不同分离株的保护。虽然一些B细胞和T细胞表位位于HIV-1蛋白的较保守区域内，但许多表位定位于可变区，并且不同病毒之间存在差异。中和B细胞应答可针对具有不同i）抗体接触残基和/或ii）蛋白质构象的病毒而变化，而T细胞应答可针对具有不同（i）T细胞受体接触残基和/或（ii）与抗原加工相关的氨基酸序列的病毒而变化。在这里，我们回顾了以前和目前的HIV-1疫苗开发策略。我们专注于圣裘德儿童研究医院（SJCRH）的研究，致力于开发HIV-1疫苗鸡尾酒策略。SJCRH多载体、多包膜疫苗现已被证明可引发HIV-1特异性B和T细胞功能，其多样性和持久性可能是预防人类HIV-1感染所需的。
A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. While some B-cell and T-cell epitopes lie within the more conserved regions of HIV-1 proteins, many are localized to variable regions and differ from one virus to the next. Neutralizing B-cell responses may vary toward viruses with different i) antibody contact residues and/or ii) protein conformations while T-cell responses may vary toward viruses with different (i) T-cell receptor contact residues and/or (ii) amino acid sequences pertinent to antigen processing. Here we review previous and current strategies for HIV-1 vaccine development. We focus on studies at St. Jude Children's Research Hospital (SJCRH) dedicated to the development of an HIV-1 vaccine cocktail strategy. The SJCRH multi-vectored, multi-envelope vaccine has now been shown to elicit HIV-1-specific B- and T-cell functions with a diversity and durability that may be required to prevent HIV-1 infections in humans.