Multiepitopic B- and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine
Multiepitopic B- and T-cell responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine
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DOI：
10.1128/jvi.74.4.1694-1703.2000
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发表时间：
2000-02-01
影响因子：
5.4
通讯作者：
Guillet, JG
中科院分区：
文献类型：
--
作者：
Gahéry-Ségard, H;Pialoux, G;Guillet, JG
我们试图开发一种抗人类免疫缺陷病毒（HIV）的脂肽疫苗与几个HIV特异性的长肽修饰的C-末端添加一个单一的棕榈酰链。制备六种衍生自调节性或结构性HIV-1蛋白（Nef、Gag和Env）的脂肽的混合物。进行I期研究以评价HIV-1血清阴性志愿者在脂肽疫苗接种中的免疫原性和耐受性，所述志愿者给予三次注射100、250或500 μ g的每种脂肽，有或没有免疫佐剂（QS 21）。本报告详细分析了疫苗接种诱导的B细胞和T细胞应答。脂肽疫苗引起强烈的和多表位的B-和T-细胞反应。接种疫苗的受试者产生识别Nef和Gag蛋白的特异性免疫球蛋白G抗体。在第三次注射后，还获得辅助性CD 4 +-T细胞应答以及特异性细胞毒性CD 8 + T细胞。这些CD 8 + T细胞能够识别天然加工的病毒蛋白。最后，还离体检测到特异性γ干扰素分泌性CD 8 + T细胞。
We have attempted to develop an anti-human immunodeficiency virus (HIV) lipopeptide vaccine with several HIV-specific long peptides modified by C-terminal addition of a single palmitoyl chain. A mixture of six lipopeptides derived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) was prepared. A phase I study was conducted to evaluate immunogenicity and tolerance in lipopeptide vaccination of HIV-1-seronegative volunteers given three injections of either 100, 250, or 500 mu g of each lipopeptide, with or without immunoadjuvant (QS21). This report analyzes in detail B- and T-cell responses induced by vaccination. The lipopeptide vaccine elicited strong and multiepitopic B- and T-cell responses. Vaccinated subjects produced specific immunoglobulin G antibodies that recognized the Nef and Gag proteins. After the third injection, helper CD4+-T-cell responses as well as specific cytotoxic CD8+ T cells were also obtained. These CD8+ T cells were able to recognize naturally processed viral proteins. Finally, specific gamma interferon-secreting CD8+ T cells were also detected ex vivo.