HIV type 1 vaccine-induced cytotoxic T cell responses in phase I clinical trials: detection, characterization, and quantitation.
HIV type 1 vaccine-induced cytotoxic T cell responses in phase I clinical trials: detection, characterization, and quantitation.
复制标题
I 期临床试验中 HIV 1 型疫苗诱导的细胞毒性 T 细胞反应：检测、表征和定量。
DOI：
10.1089/aid.1997.13.211
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发表时间：
1997
影响因子：
1.5
通讯作者：
Weinhold,KJ
中科院分区：
文献类型：
--
作者：
McElrath,MJ;Siliciano,RF;Weinhold,KJ
自1990年AIDS疫苗评估组（AVEG）I期临床试验开始以来，检测HIV-1疫苗特异性CD 8 + MHC I类限制性CTL应答的研究一直是几个实验室的重点。这些发现的总结见表1。在迄今为止测试的最初14种候选疫苗中，大多数是重组包膜亚单位免疫原，旨在引发病毒中和抗体。虽然这些制剂中的一些刺激了对疫苗免疫原和异源HIV-1菌株的体液应答，但仅在极少数情况下检测到CTL反应性。即使使用新的佐剂，显着提高动物模型中的CTL反应（即，QS 21）未能增加罕见的CTL反应活性，在人体I期试验中看到这些基于疫苗的亚单位疫苗。在两项涉及重组痘病毒包膜免疫原（即AVEG 010和AVEG 012）的已完成试验中，与先前试验相比，疫苗中CTL应答的频率显著增加。受这些结果的鼓舞，研究已经开始使用下一代痘病毒载体，其含有额外的HIV-1基因，例如编码Gag蛋白的基因，其在感染细胞中的表位表达代表了感染患者中CD 8 + CTL的主要靶标。希望这些试验，以及未来对含有env、gag、pol和nef基因的载体的研究，将导致在疫苗中更高频率的可检测的CTL应答和更广泛的CTL库。
Investigations to detect HIV-1 envelope-specific CD8+ MHC class I-restricted CTL responses in HIV-uninfected vaccine re-cipients have been the focus of several laboratories since the initiation of AIDS Vaccine Evaluation Group (AVEG) phase I clinical trials in 1990.2" 5 A summary of these findings is presented in Table 1. Of the initial 14 candidate vaccines tested to date, most have been recombinant envelope subunit immunogens, designed to elicit virus-neutralizing antibodies. While some of these formulations stimulated humoral responses to the vaccine immunogen and heterologous HIV-1 strains, CTL re-activities were detected only in rare instances. Even the use of novel adjuvants that significantly enhanced CTL responses in animal models (ie, QS21) failed to increase the rare CTL re-activities seen in human phase I trials of these envelope-based subunit vaccines. In two completed trials involving recombi-nant poxvirus-based envelope immunogens (ie, AVEG 010 and AVEG 012), the frequency of CTL responses in vaccinées was increased significantly in comparison to previous trials. 6Encouraged by these results, studies have begun with the next generation of poxvirus vectors, which contain additional HIV-1 genes such as those encoding the Gag protein, whose epitope expression in infected cells represents a major target of CD8+ CTLs in infected patients. It is hoped that these trials, in addition to future studies with vectors containing env, gag, pol, and nef genes, will result in still higher frequencies of detectable CTL responses and a broader CTL repertoire among vaccine