DEVELOPMENT OF A MONKEY MODEL FOR TESTING OF ANTIVIRAL AGENTS AGAINST HIV1

开发用于测试 HIV1 抗病毒药物的猴子模型

• 批准号: 6101180
• 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/6101180
• 关键词: AIDS therapy; AIDS vaccines; Macaca nemestrina; antibody titering; disease /disorder model; human immunodeficiency virus 1; longitudinal animal study; model design /development; neutralizing antibody; nonhuman therapy evaluation; recombinant virus; simian immunodeficiency virus; virus DNA; virus infection mechanism; virus replication

A good animal model for HIV-1 is essential for AIDS vaccine studies and development of efficacious anti-viral agents. Pig-tailed macaques have been found to be susceptible to HIV-1 infection (Agy, et al., 1992). Based upon this initial report, we previously infected 2 pig-tailed macaques (designated as PT86 and PT99) with HIV-1/LAI and have monitored long-term infection and clinical changes. Each animal responded uniquely to the infection. In the case of PT86 viral sequences (DNA and RNA) were detected in the PBMC in the first year whereas the lymph nodes were positive even at 3 years P.I. Antibodies to HIV-1 gag and env proteins have persisted in PT86 at 5 years post-infection although a decrease in the gag antibodies was seen. The CD4+/CD8+ ratio continues to gradually decline. In the case of PT99 viral DNA sequences were seen in the PBMCs up to 1 year and in the lymph node 3 years PI. Antibodies to the env proteins have persisted at 5 year PI. The CD4+/CD8+ ratio remained stable. No clinical symptoms have developed in PT86 or PT99. Since the clinical symptoms of AIDS in humans generally develop in 5-10 years and developed after about 10 years post-infection in one chimpanzee, it is most likely too early to see clinical symptoms in the infected pig-tailed macaques. The results thus far indicate that HIV-1 infection of pig-tailed macaques may be similar to the infection seen in some humans: in the case of PT99 the infection is non-progressing whereas PT86 might represent a long-term survivor. The pig-tailed macaque model will be used to evaluate protection by HIV-1 plasmid DNA vaccine against homologous challenge virus infection (HIV-1/LAI).

一个好的HIV-1动物模型对于艾滋病疫苗研究和 开发有效的抗病毒药物。猪尾猕猴有 被发现对艾滋病毒-1感染敏感(Agy等人，1992年)。 根据这份初步报告，我们之前感染了2只猪尾巴 携带HIV-1/LAI的猕猴(编号为PT86和PT99)，并已监测到 长期感染和临床变化。每只动物都有独特的反应 对感染的影响。在PT86病毒序列(DNA和RNA)的情况下 在第一年的PBMC中检测到，而淋巴结是 即使在3岁时HIV-1 Gag和env蛋白的P.I.抗体也呈阳性 在感染后5年仍保持在PT86中，尽管 出现了呕吐抗体。CD_4~+/CD_8~+比值继续逐渐升高 拒绝。在PT99的情况下，在PBMC中发现了病毒DNA序列 最长可达1年，在淋巴结内可达3年。针对环境的抗体 蛋白质在5年等电点上持续存在。CD4+/CD8+比值保持不变 稳定。PT86或PT99没有出现临床症状。自.以来 人类艾滋病的临床症状一般在5-10年内出现， 它是在一只黑猩猩感染后大约10年后开发出来的 在感染者身上看到临床症状很可能还为时过早 猪尾猕猴。到目前为止的结果表明，艾滋病毒-1感染 猪尾猕猴的感染可能与某些 人类：PT99感染是无进展的，而PT86感染是无进展的 可能代表着一个长期的幸存者。 猪尾猕猴模型将用于评估保护措施 针对同源挑战病毒感染的HIV-1质粒DNA疫苗 (HIV-1/LAI)。