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: 7732732
• 负责人: John R Mascola
• 金额: $ 30.51万
• 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/7732732
• 关键词: AIDS Vaccines; Adenoviruses; Antibodies; Antigens; Biology; CD4 Positive T Lymphocytes; Cellular Immunity; Chronic; Disease; Disease-Free Survival; Dose; Evaluation; Gagging; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; HIV-1 vaccine; 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; pol genes; protective effect; research clinical testing; simian human immunodeficiency virus; vaccine efficacy

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

疫苗诱导的细胞免疫可以控制猴免疫缺陷病毒（SIV）感染猴子的病毒复制，尽管病毒控制的水平和持久性不是最佳的。我们之前证明，用质粒DNA免疫猴子，然后用编码SIV蛋白的复制缺陷腺病毒载体免疫猴子，可以减少病毒血症，延长存活时间。这种生存与保留的中枢记忆CD4+ T淋巴细胞有关，并且可以通过疫苗诱导的细胞免疫反应的大小来预测。疫苗效力的这些免疫相关因素应指导人类艾滋病疫苗的评价。此外，本研究的结果表明，设定值病毒载量和总CD4+ T淋巴细胞计数可能不能完全预测疫苗的效果。