Comparative efficacy of subtype AE simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques
Comparative efficacy of subtype AE simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques
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DOI：
10.1128/jvi.01727-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
--
作者：
De Rose, Robert;Batten, C. Jane;Kent, Stephen J.
人类免疫缺陷病毒（HfV）毒株之间的巨大差异阻碍了艾滋病疫苗接种。基于异种B亚型的猴-人免疫缺陷病毒（SHIV）DNA初免和痘病毒加强疫苗方案可诱导猕猴部分T细胞介导的保护性免疫。我们分析了一组DNA，重组禽痘病毒（FPV），和牛痘病毒（VV）表达亚型AE HIV 1型（HIV-1）达特，Rev和Env蛋白和SIV Gag/Pol在30猪尾猕猴。SIN GAG特异性的CD 4和CD 8 T细胞应答由连续DNA/FPV疫苗接种诱导，尽管较低的FPV剂量、VV/FPV疫苗接种和单独DNA疫苗的免疫原性并不一致。SHIV AE DNA初免、FPV加强方案的免疫原性显著低于可比的B亚型SHIN疫苗接种。在强毒B亚型SHIV攻击后，AE亚型SHIV免疫动物的峰值病毒载量适度低于对照组（0.4 log（10）拷贝/ml）。与B亚型SHIV疫苗接种猕猴相比，AE亚型对持续高水平病毒血症和CD 4 T细胞耗竭的保护作用较低。Gag在疫苗接种后比其他AE亚型SHIV疫苗蛋白具有高度免疫显性，并且这种免疫显性在攻击后加剧。有趣的是，较低水平的免疫反应引发并没有钝化攻击后的GAG特异性回忆反应，尽管更温和的保护。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，但不同亚型疫苗的免疫原性差异和广泛的跨亚型保护是重大障碍。
Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HfV) 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. SIN 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 SHIN vaccination. Peak viral load was modestly (0.4 log(10) 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.