Non Human Primate Models of SIV and HIV Immune Protection

SIV 和 HIV 免疫保护的非人灵长类动物模型

• 批准号: 8336367
• 负责人: John Mascola
• 金额: $ 33.08万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336367
• 关键词: AIDS Vaccines; Adenoviruses; Affect; Antibodies; Antigens; CD4 Positive T Lymphocytes; Cellular Immunity; Chronic; Data; Data Analyses; Disease-Free Survival; Dose; Evaluation; Gagging; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; Human; Immune; Immune response; Immunization; Immunologic Deficiency Syndromes; Individual; Infection; Lymphocyte Count; Measures; Mediating; Modeling; Monkeys; Phase; Physiological; Population; Recombinants; SIV; Serotyping; T-Lymphocyte; Testing; Vaccines; Viral; Viral Antigens; Viral Load result; Viral Proteins; Viremia; Virus; Work; defective adenoviral vector; design; in vivo; memory CD4 T lymphocyte; nonhuman primate; plasmid DNA; protective effect; research clinical testing; vaccine candidate; vaccine efficacy; vaccine-induced immunity

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.

疫苗诱导的细胞免疫可以控制邻肌免疫缺陷病毒（SIV）感染的猴子中的病毒复制，尽管病毒控制的水平和持久性并不最佳。 我们先前证明，用质粒DNA的猴子免疫，然后复制有缺陷的腺病毒载体编码SIV蛋白的腺病毒载体导致病毒血症的降低和长期存活率。该存活与保存的中央记忆CD4+ T淋巴细胞有关，可以通过疫苗诱导的细胞免疫反应的大小来预测。 疫苗功效的这些免疫相关性应指导人类艾滋病疫苗的评估。此外，这项研究的结果表明，设定点病毒负荷和总CD4+ T淋巴细胞计数可能无法完全预测疫苗效应。 上述研究结合了几种SIV抗原：Env，GAG和POL。在一项正在进行的研究中，我们通过相同的组合或单独使用ENV或单独使用GAG-POL对猴子进行免疫，以确定每种疫苗免疫原的个体效应。结果表明，GAG-POL和ENV都对病毒载量产生了保护作用，并且这些作用很可能是T细胞介导的。 Env Plus GAG-POL的组合效果比任何一个人都更好。其他正在进行的研究将测试重组腺病毒的几种替代血清型的影响 此外，我们目前正在进行研究以开发SIV的低剂量粘膜挑战模型 - 这可能是人类HIV感染的更生理模型。这些研究的初步数据表明，疫苗诱导的免疫力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。