Gahéry-Ségard H, Pialoux G, Charmeteau B, Sermet S, Poncelet H, Raux M, Tartar A, Lévy J P, Gras-Masse H, Guillet J G
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM Unit¿e 445, Institut Cochin de G¿en¿etique Mol¿eculaire, Universit¿e Ren¿ee Descartes, H¿opital Cochin, 75014 Paris, France.
J Virol. 2000 Feb;74(4):1694-703. doi: 10.1128/jvi.74.4.1694-1703.2000.
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 microg 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.
我们试图研发一种抗人类免疫缺陷病毒（HIV）脂肽疫苗，该疫苗含有几种经C末端添加单个棕榈酰链修饰的HIV特异性长肽。制备了一种由源自HIV-1调节蛋白或结构蛋白（Nef、Gag和Env）的六种脂肽组成的混合物。开展了一项I期研究，以评估HIV-1血清阴性志愿者接种脂肽疫苗后的免疫原性和耐受性，这些志愿者接受了三次注射，每次注射100、250或500微克的每种脂肽，有或没有免疫佐剂（QS21）。本报告详细分析了接种疫苗后诱导的B细胞和T细胞反应。脂肽疫苗引发了强烈且多表位的B细胞和T细胞反应。接种疫苗的受试者产生了识别Nef和Gag蛋白的特异性免疫球蛋白G抗体。第三次注射后，还获得了辅助性CD4(+) T细胞反应以及特异性细胞毒性CD8(+) T细胞。这些CD8(+) T细胞能够识别天然加工的病毒蛋白。最后，在体外也检测到了分泌特异性γ干扰素的CD8(+) T细胞。
