MOLECULAR APPROACHES FOR DEVELOPMENT OF AN HIV VACCINE--RHESUS MACAQUES MODEL

HIV疫苗开发的分子方法——恒河猴模型

• 批准号: 3774896
• 负责人: G FRANCHINI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/3774896
• 关键词: AIDS vaccines; HIV infections; Macaca mulatta; Salmonella typhimurium; active immunization; attenuated microorganism; disease /disorder model; drug delivery systems; drug screening /evaluation; genes; human immunodeficiency virus 1; human immunodeficiency virus 2; human tissue; simian immunodeficiency virus; vaccinia virus; virus antigen

This project is a continuation from last year. Its aim is to test in rhesus macaques the potency of various live vectors carrying human immunodeficiency virus type 1 (HIV-1), HIV-2 and simian immunodeficiency virus (SIV) antigens in eliciting a protective immunoresponse. Three different delivery systems have been tested: 1) attenuated vaccinia, 2) avipox, and 3) attenuated Salmonella typhimurium strain as a bacterial vaccine, carrying HIV/SIV antigens. The immunoresponse in the immunized animals will be further stimulated by using purified viral antigens (either native or recombinant viral subunits). Rhesus macaques, which are susceptible to the infection of both SIV(mac251) and HIV-2, will be used. The end point of these studies will be the protection from infection by either SIV or HIV-2. Vectors containing HIV-1 antigens will also be evaluated for their immunogenicity in rhesus macaques. The animals immunized with SIV/HIV-2 recombinant vectors have been challenged with live virus twice at six months apart. The results indicate that NYVAC recombinant vaccines are better immunogens than ALVAC and recombinant Salmonella and provide long lasting protection without need of further boosts. Another aspect of prevention of viral infection has been investigated using phosphorothioated oligonucleotides against HIV-1 auxillary genes (vpr and vif). Further information on the biological importance of the HIV-2 auxillary genes in vitro and in vivo has also been obtained.

这个项目是去年的延续。 其目的是测试 恒河猴 携带人类的各种活载体的效力 免疫缺陷病毒 1 型 (HIV-1)、HIV-2 和猿猴免疫缺陷 病毒（SIV）抗原引发保护性免疫反应。 三 已测试不同的输送系统：1) 减毒牛痘，2) 禽痘，和 3) 减毒鼠伤寒沙门氏菌菌株 疫苗，携带 HIV/SIV 抗原。 免疫者的免疫反应 使用纯化的病毒抗原将进一步刺激动物 （天然或重组病毒亚基）。 恒河猴，它们是 易感染 SIV(mac251) 和 HIV-2，将使用。 这些研究的终点将是防止感染 SIV 或 HIV-2。 含有 HIV-1 抗原的载体也将被 评估了它们在恒河猴中的免疫原性。 动物们 用 SIV/HIV-2 重组载体免疫的人受到以下挑战 两次活病毒，间隔六个月。 结果表明 NYVAC 重组疫苗是比 ALVAC 和重组疫苗更好的免疫原 沙门氏菌并提供持久的保护，无需进一步 提升。 预防病毒感染的另一个方面是 研究使用硫代磷酸寡核苷酸对抗 HIV-1 辅助基因（vpr 和 vif）。 有关生物的更多信息 HIV-2辅助基因在体外和体内的重要性也已得到证实 获得。