DNA gag/adenovirus type 5 (Ad5) gag and Ad5 gag/Ad5 gag vaccines induce distinct T-cell response profiles
DNA gag/adenovirus type 5 (Ad5) gag and Ad5 gag/Ad5 gag vaccines induce distinct T-cell response profiles
复制标题
DOI：
10.1128/jvi.00620-08
复制
发表时间：
2008-08-01
影响因子：
5.4
通讯作者：
Casimiro, Danilo R.
中科院分区：
文献类型：
--
作者：
Cox, Kara S.;Clair, James H.;Casimiro, Danilo R.
默克公司II期5型腺病毒（Ad 5）gag/pol/nef概念试验的结果表明，该疫苗在高危人群中对人类免疫缺陷病毒（HIV）感染缺乏有效性。在这一结果之后要探讨的许多问题中，有（i）Ad 5疫苗是否诱导了有效性所必需的T细胞应答的质量，以及（ii）Ad 5疫苗缺乏有效性是否可以推广到旨在诱导HIV 1型（HIV-1）特异性T细胞应答的其他载体方法。在这里，我们提出了一个全面的评估的T细胞反应谱从队列的临床试验受试者谁收到了HIV CAM-1 gag插入交付的方案与DNA引发随后的Ad 5加强（n = 50）或同源的Ad 5/Ad 5的prime-boost方案（n = 70）。使用统计学合格的九色细胞内细胞因子染色测定法检测样品，测量白细胞介素-2（IL-2）、肿瘤坏死因子α、巨噬细胞炎性蛋白1 β和γ干扰素的产生和CD 107 a的表达。两种疫苗方案均诱导了CD 4（+）和CD 8（+）HIV gag特异性T细胞应答，这些T细胞应答可表达几种细胞内标志物。观察到几种趋势，其中DNA/Ad 5队列中HIV-1特异性CD 4（+）T细胞和抗原特异性CD 8（+）T细胞产生IL-2的频率比Ad 5/Ad 5队列更明显。将讨论这些结果对未来疫苗开发的影响。
Results from Merck's phase II adenovirus type 5 (Ad5) gag/pol/nef test-of-concept trial showed that the vaccine lacked efficacy against human immunodeficiency virus (HIV) infection in a high-risk population. Among the many questions to be explored following this outcome are whether (i) the Ad5 vaccine induced the quality of T-cell responses necessary for efficacy and (ii) the lack of efficacy in the Ad5 vaccine can be generalized to other vector approaches intended to induce HIV type 1 (HIV-1)-specific T-cell responses. Here we present a comprehensive evaluation of the T-cell response profiles from cohorts of clinical trial subjects who received the HIV CAM-1 gag insert delivered by either a regimen with DNA priming followed by Ad5 boosting (n = 50) or a homologous Ad5/Ad5 prime-boost regimen (n = 70). The samples were tested using a statistically qualified nine-color intracellular cytokine staining assay measuring interleukin-2 (IL-2), tumor necrosis factor alpha, macrophage inflammatory protein 1 beta, and gamma interferon production and expression of CD107a. Both vaccine regimens induced CD4(+) and CD8(+) HIV gag-specific T-cell responses which variably expressed several intracellular markers. Several trends were observed in which the frequencies of HIV-1-specific CD4(+) T cells and IL-2 production from antigen-specific CD8(+) T cells in the DNA/Ad5 cohort were more pronounced than in the Ad5/Ad5 cohort. Implications of these results for future vaccine development will be discussed.