Development of a monkey model for testing antiviral

开发用于测试抗病毒药物的猴子模型

• 批准号: 6678842
• 负责人: Arifa S Khan
• 金额: --
• 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/6678842
• 关键词: AIDS therapy; AIDS vaccines; CD antigens; Macaca nemestrina; cell population study; disease /disorder model; gene expression; human immunodeficiency virus 1; immunogenetics; immunomodulators; immunoregulation; immunotherapy; longitudinal animal study; lymphocyte; model design /development; nonhuman therapy evaluation; polymerase chain reaction; vector vaccine; virus diseases; virus infection mechanism

Summary: A good animal model for HIV-1 is essential for AIDS vaccine studies and development of efficacious anti-viral agents. Additionally, such a model will provide insight into the mechanism of correlates of virus infection and protection. We have obtained reproducible, long-term HIV-1 infection in pig-tailed macaques and have evaluated virus infection in animals that received high and low doses of HIV-1/LAI. Although, each animal responded uniquely to the infection, in all cases HIV-1 antibodies developed and viral sequences were detected in the PBMCs. No significant clinical symptoms were seen. The results of our study indicate that pig-tailed macaques may be a useful animal model for evaluating the efficacy of novel vaccine strategies. To investigate whether pig-tailed macaques are a good animal model for vaccine studies, we tested the efficacy of the DNA prime with protein boost strategy using our HIV-1 DNA vaccines with subsequent Env protein boost against challenge with homologous virus (HIV-1/LAI). Virus could not be detected in the plasma of animals immunized with a vaccine DNA containing the CMV promoter. PBMC DNA was analyzed by PCR using pol and gag primers to further evaluate virus infection. The results indicate that pig-tailed macaques can be used to demonstrate the efficacy of immunization strategies using HIV/LAI based vaccines against homologous challenge virus.

摘要：良好的 HIV-1 动物模型对于艾滋病疫苗研究和有效抗病毒药物的开发至关重要。此外，这样的模型将提供对病毒感染和保护的相关机制的深入了解。我们在猪尾猕猴中获得了可重复的长期 HIV-1 感染，并评估了接受高剂量和低剂量 HIV-1/LAI 的动物的病毒感染情况。尽管每只动物对感染的反应各不相同，但在所有情况下，HIV-1 抗体均产生，并且在 PBMC 中检测到病毒序列。未见明显临床症状。我们的研究结果表明，猪尾猕猴可能是评估新型疫苗策略功效的有用动物模型。 为了调查猪尾猕猴是否是疫苗研究的良好动物模型，我们使用 HIV-1 DNA 疫苗和随后的 Env 蛋白加强来对抗同源病毒 (HIV-1/LAI) 的攻击，测试了 DNA 初免和蛋白加强策略的功效。用含有 CMV 启动子的疫苗 DNA 免疫的动物血浆中无法检测到病毒。使用 pol 和 gag 引物通过 PCR 分析 PBMC DNA，以进一步评估病毒感染。结果表明，猪尾猕猴可用于证明使用基于 HIV/LAI 的疫苗针对同源攻击病毒的免疫策略的有效性。