Dale C J, De Rose R, Stratov I, Chea S, Montefiori D C, Thomson S, Ramshaw I A, Coupar B E H, Boyle D B, Law M, Kent S J
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
J Virol. 2004 Dec;78(24):13819-28. doi: 10.1128/JVI.78.24.13819-13828.2004.
Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIV(mn229) correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.
在理解T细胞免疫对艾滋病的保护作用方面仍需进一步进展。我们分析了一组多基因猿猴/人类免疫缺陷病毒（SHIV）DNA和禽痘病毒启动及加强疫苗在远交猪尾猕猴中的免疫原性和保护效果。还研究了所需的疫苗接种次数、单独DNA疫苗接种的效果以及禽痘病毒加强疫苗共表达细胞因子（γ干扰素）的效果。通过先后接种DNA疫苗和禽痘病毒疫苗，可协同诱导高水平的广泛反应性CD4和CD8 T细胞免疫反应。利用共表达γ干扰素的禽痘病毒、单次DNA启动疫苗接种或单独的DNA疫苗的方案的免疫原性较差。尽管失去了SHIV特异性增殖T细胞，但仍观察到对强毒株SHIV攻击的显著控制。强毒株SHIV（mn229）攻击的结果与疫苗免疫原性相关，只是单独的DNA疫苗接种引发保护的效果几乎与DNA/禽痘病毒方案一样有效，尽管通过标准检测其免疫原性可忽略不计。这些研究表明，用DNA疫苗和禽痘病毒疫苗启动免疫可能会延缓人类艾滋病的发展。
