Development of a monkey model for testing antiviral

摘要：良好的HIV-1动物模型对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相关因素的机制的洞察。我们已经在猪尾猕猴中获得了可重复的、长期的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。虽然，每种动物对感染的反应都是独特的，但在所有情况下，都会产生HIV-1抗体，并在PBMC中检测到病毒序列。未见明显的临床症状。我们的研究结果表明，猪尾猕猴可能是一个有用的动物模型来评估新的疫苗策略的有效性。 为了调查猪尾猕猴是否是疫苗研究的良好动物模型，我们使用我们的HIV-1 DNA疫苗和随后的Env蛋白Boost来测试DNA Prime with Protein Boost策略的有效性，以抵御同源病毒(HIV-1/LAI)的攻击。用含有CMV启动子的疫苗DNA免疫的动物，在血浆中检测不到病毒。采用聚合酶链式反应(Poll)和聚合酶链式反应(Gag)对PBMC DNA进行分析，以进一步评估病毒感染情况。结果表明，猪尾猕猴可以用来证明基于HIV/LAI的疫苗对同源挑战病毒的免疫策略的有效性。

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.