Non Human Primate Models of SIV and HIV Immune Protection

疫苗诱导的细胞免疫可以控制感染猴免疫缺陷病毒(SIV)的猴子的病毒复制，尽管病毒控制的水平和持久性并不是最优的。我们以前曾证明，用编码SIV蛋白的复制缺陷型腺病毒载体和质粒DNA免疫猴子，可以减少病毒血症，延长存活时间。这种存活率与保存的中央记忆的CD4+T淋巴细胞有关，并可以通过疫苗诱导的细胞免疫反应的大小来预测。这些疫苗效力的免疫相关性应该指导艾滋病疫苗在人类身上的评估。此外，这项研究的结果表明，设定的病毒载量和CD4+T淋巴细胞总数可能不能完全预测疫苗的效果。 上述研究使用了几种SIV抗原的组合：Env、GAG和POL。在一项正在进行的研究中，我们用同样的组合免疫猴子，或者单独使用Env，或者单独使用Gag-Pol，以确定每种疫苗免疫原的单独效果。结果表明，Gag-Pol和Env对病毒载量均有保护作用，且这些作用很可能是由T细胞介导的。Env加Gag-Pol的组合比单独使用效果更好。其他正在进行的研究将测试几种不同血清型的重组腺病毒的效果。 此外，我们目前正在进行研究，以开发一种针对SIV的低剂量黏膜攻击模型-这可能是一个更具生理学意义的人类HIV感染模型。这些研究的初步数据表明，疫苗诱导免疫可以降低感染的变化。对这些数据的广泛分析，包括对感染的免疫相关性的分析，正在进行中。

Vaccine-induced cellular immunity can control viral replication in simian immunodeficiency virus (SIV)-infected monkeys, though the level and persistence of viral control is not optimal. We previously demonstrated that immunization of monkeys with plasmid DNA followed by replication defective adenoviral vectors encoding SIV proteins led to a reduction in viremia and prolonged survival. This survival was associated with preserved central memory CD4+ T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans. In addition, the results of the this study indicated that set point viral load and total CD4+ T lymphocyte count may not be fully predictive of a vaccine effect. The studies described above used a combination of several SIV antigens: Env, Gag and Pol. In an ongoing study, we immunized monkeys with this same combination, or with Env alone, or Gag-Pol alone, to determine the individual effect of each vaccine immunogen. The results indicate that both Gag-Pol and Env contribute to a protective effect on viral load and that these effects are most likely T-cell mediated. The combination of Env plus Gag-Pol worked better than either alone. Other ongoing studies will test the effect of several alternative serotypes of recombinant adenovirus In addition, we are currently performing studies to develop a low dose mucosal challenge model for SIV - which may be a more physiological model of human HIV infection The preliminary data from these studies shows that vaccine induced immunity can lower the change of infection. And extensive analysis of these data, including an analysis of immune correlates of infection, are ongoing.