Conserved HIV Epitopes for an Effective HIV Vaccine.
Conserved HIV Epitopes for an Effective HIV Vaccine.
复制标题
DOI：
10.4172/2155-9899.1000518
复制
发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Yamamoto, Janet K
中科院分区：
文献类型：
--
作者：
Sahay, Bikash;Nguyen, Cuong Q;Yamamoto, Janet K
尽管在针对HIV-1的抗逆转录病毒疗法方面取得了重大进展，但迫切需要有效的HIV疫苗来减少世界上新的HIV感染病例。疫苗是控制和预防艾滋病毒/艾滋病等传染病传播的最重要的医疗工具。过去几次失败的针对HIV-1的IIb至III期临床疫苗试验产生了大量信息，可用于更好地设计未来有效的HIV疫苗。大多数测试的候选疫苗对HIV蛋白产生强烈的体液应答;然而，由于以下原因未能提供保护：1）HIV-1中和抗体和HIV特异性抗体依赖性Fc介导的效应子活性的低水平和窄宽度，2）抗HIV T细胞应答的低水平和差质量，3）对免疫显性非保护性HIV表位的过度应答，在某些情况下阻断了保护性免疫和/或增强了HIV感染。HIV B细胞抗原表位已被广泛研究，用于产生抗HIV的广谱中和抗体（bNAb），下一步是开发用于HIV疫苗的bNAb抗原表位免疫原。bNAb表位通常是构象表位，因此更难以构建为疫苗免疫原，并且可能包括免疫显性非保护性HIV表位。相比之下，T细胞表位是短的线性肽，其更容易构建成不含免疫显性非保护性表位的疫苗免疫原。然而，其困难在于识别HIV亚型中保守的T细胞表位并诱导持久的、有效的多功能T细胞和细胞毒性T淋巴细胞（CTL）抗HIV活性。此外，这些保护性T细胞表位必须被疫苗试验靶向国家中流行的HLA识别。总之，从以前的疫苗试验的结果延伸，未来的疫苗应该结合联合收割机的T-和B-细胞表位作为疫苗免疫原，以诱导大量的广泛和有效的免疫效应活性所需的杀菌保护对全球艾滋病毒亚型。
Despite major advances in antiretroviral therapy against HIV-1, an effective HIV vaccine is urgently required to reduce the number of new cases of HIV infections in the world. Vaccines are the ultimate tool in the medical arsenal to control and prevent the spread of infectious diseases such as HIV/AIDS. Several failed phase-IIb to -III clinical vaccine trials against HIV-1 in the past generated a plethora of information that could be used for better designing of an effective HIV vaccine in the future. Most of the tested vaccine candidates produced strong humoral responses against the HIV proteins; however, failed to protect due to: 1) the low levels and the narrow breadth of the HIV-1 neutralizing antibodies and the HIV-specific antibody-dependent Fc-mediated effector activities, 2) the low levels and the poor quality of the anti-HIV T-cell responses, and 3) the excessive responses to immunodominant non-protective HIV epitopes, which in some cases blocked the protective immunity and/or enhanced HIV infection. The B-cell epitopes on HIV for producing broadly neutralizing antibodies (bNAbs) against HIV have been extensively characterized, and the next step is to develop bNAb epitope immunogen for HIV vaccine. The bNAb epitopes are often conformational epitopes and therefore more difficult to construct as vaccine immunogen and likely to include immunodominant non-protective HIV epitopes. In comparison, T-cell epitopes are short linear peptides which are easier to construct into vaccine immunogen free of immunodominant non-protective epitopes. However, its difficulty lies in identifying the T-cell epitopes conserved among HIV subtypes and induce long-lasting, potent polyfunctional T-cell and cytotoxic T lymphocyte (CTL) activities against HIV. In addition, these protective T-cell epitopes must be recognized by the HLA prevalent in the country(s) targeted for the vaccine trial. In conclusion, extending from the findings from previous vaccine trials, future vaccines should combine both T- and B-cell epitopes as vaccine immunogen to induce multitude of broad and potent immune effector activities required for sterilizing protection against global HIV subtypes.