Division of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland.
Eur J Immunol. 2012 Nov;42(11):3038-48. doi: 10.1002/eji.201242696. Epub 2012 Oct 1.
We report the results of the Theravac-01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus-based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC-B vaccine was injected intra-muscularly into ten HIV-infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV-specific T-cell responses following immunization were quantitatively analyzed using an IFN-γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC-B vaccine is safe and highly immunogenic, as indicated by increased HIV-specific T-cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T-cell responses, and the appearance of newly detected HIV-specific CD4(+) and CD8(+) T-cell responses were observed. Furthermore, immunization mostly induced an increase in Gag-specific T-cell responses. In conclusion, NYVAC-B immunization induces broad, vigorous, and polyfunctional HIV-specific T-cell responses, suggesting that poxvirus-based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.
我们报告了 Theravac-01 期 I 临床试验的结果，该试验旨在评估一种基于痘病毒的载体 NYVAC 的安全性和免疫原性，该载体表达来自 HIV 分离株 B 的 Gag、Pol、Nef 和 Env。NYVAC-B 疫苗通过肌肉注射接种给 10 名成功接受抗逆转录病毒治疗的 HIV 感染患者，在第 0 天和第 4 周各接种两次。在 48 周内监测安全性和免疫原性。通过 IFN-γ ELISPOT 分析定量分析免疫接种后的 HIV 特异性 T 细胞反应，并通过多色流式细胞术定性分析其功能谱（包括多种细胞因子分泌以及细胞毒性和增殖能力）。我们的结果表明，NYVAC-B 疫苗是安全且高度免疫原性的，几乎所有疫苗接种者的 HIV 特异性 T 细胞反应均增加。有趣的是，观察到既有 T 细胞反应的扩增，也有新检测到的 HIV 特异性 CD4(+)和 CD8(+)T 细胞反应的出现。此外，免疫接种主要诱导 Gag 特异性 T 细胞反应的增加。总之，NYVAC-B 免疫接种诱导广泛、强烈和多功能的 HIV 特异性 T 细胞反应，表明痘病毒疫苗方案可能在治疗性 HIV 疫苗领域具有重要作用。
