De Rose Robert, Batten C Jane, Smith Miranda Z, Fernandez Caroline S, Peut Viv, Thomson Scott, Ramshaw Ian A, Coupar Barbara E H, Boyle David B, Venturi Vanessa, Davenport Miles P, Kent Stephen J
Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
J Virol. 2007 Jan;81(1):292-300. doi: 10.1128/JVI.01727-06. Epub 2006 Oct 18.
Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.
人类免疫缺陷病毒（HIV）毒株之间的巨大差异阻碍了艾滋病疫苗的研发。基于异源B亚型的猿猴免疫缺陷病毒（SHIV）DNA初免和痘病毒加强疫苗方案可在猕猴中诱导部分由T细胞介导的保护性免疫。我们分析了一组在30只猪尾猕猴中表达1型AE亚型HIV（HIV-1）Tat、Rev和Env蛋白以及SIV Gag/Pol的DNA、重组禽痘病毒（FPV）和痘苗病毒（VV）。连续进行DNA/FPV疫苗接种可诱导SIV Gag特异性CD4和CD8 T细胞反应，不过较低剂量的FPV、VV/FPV疫苗接种以及单独的DNA疫苗免疫原性并不一致。与可比的B亚型SHIV疫苗接种相比，SHIV AE DNA初免、FPV加强方案的免疫原性显著较低。在受到强毒力B亚型SHIV攻击后，与对照组相比，AE亚型SHIV免疫动物的病毒载量峰值适度降低（0.4 log10拷贝/毫升）。与B亚型SHIV疫苗接种的猕猴相比，AE亚型对持续性高病毒血症和CD4 T细胞耗竭的保护作用较小。接种疫苗后，Gag在其他AE亚型SHIV疫苗蛋白中具有高度免疫优势，攻击后这种免疫优势更加明显。有趣的是，尽管保护作用较为适度，但免疫反应的较低启动水平并未减弱攻击后Gag特异性回忆反应。这些研究表明，启动T细胞免疫以预防人类艾滋病是可能的，但各种亚型疫苗免疫原性的差异以及广泛的跨亚型保护是巨大的障碍。
