Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials.
Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials.
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DOI：
10.1016/j.vaccine.2015.03.036
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发表时间：
2015-05-11
期刊：
影响因子：
5.5
通讯作者：
Keefer, Michael C.
中科院分区：
文献类型：
--
作者：
Jin, Xia;Morgan, Cecilia;Yu, Xuesong;DeRosa, Stephen;Tomaras, Georgia D.;Montefiori, David C.;Kublin, James;Corey, Larry;Keefer, Michael C.
质粒DNA疫苗因其优异的免疫原性已被许可用于家养动物，但尚未被许可用于人类。在这里，我们报告了一个回顾性分析1218名健康的人类志愿者参加了10个I期临床试验中，编码HIV抗原的DNA质粒管理。通过经验证的用HIV肽池刺激的细胞内细胞因子染色（ICS）来定量引发的T细胞免疫应答。还使用经验证的测定法分析了HIV特异性结合和中和抗体活性。结果显示，在没有佐剂和用替代疫苗加强免疫的情况下，DNA疫苗分别在平均13.3%（95%CI：9.8%至17.8%）和37.7%（95%CI：31.9%至43.8%）的疫苗接受者中引发了CD8+和CD4+ T细胞应答。三次疫苗接种（相对于2次）提高了具有抗原特异性CD8+应答的受试者比例（p=0.02），增加DNA剂量也是如此（p=0.007）。此外，女性和体重指数较低的参与者与较高的CD4+ T细胞应答率独立相关（分别为p=0.001和p=0.008）。这些疫苗引起最小的中和和结合抗体应答。这些HIV DNA疫苗在人体内的免疫原性研究结果可为今后的临床试验提供指导。
Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8% to 17.8%) and 37.7% (95% CI: 31.9% to 43.8%) of vaccine recipients, respectively. Three vaccinations (versus 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower Body Mass Index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials.
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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