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

这个项目是去年的延续。它的目的是在 恒河猴对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)抗原在诱导保护性免疫反应中的作用。三 已经测试了不同的递送系统：1)减毒牛痘，2) 禽痘，以及3)减毒鼠伤寒沙门氏菌作为细菌 携带艾滋病毒/SIV抗原的疫苗。免疫后机体的免疫应答 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 易受SIV(Mac251)和HIV-2感染的药物将被使用。 这些研究的终点将是预防感染 不是SIV就是HIV-2。含有HIV-1抗原的载体也将被 对它们在恒河猴体内的免疫原性进行了评估。动物们 用SIV/HIV-2重组载体免疫的人感染了 相隔六个月两次活病毒。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，不需要进一步 助推器。预防病毒感染的另一个方面是 应用硫代寡核苷酸抗HIV-1的研究 辅助基因(vpr和vif)。关于生物的进一步信息 HIV-2辅助基因在体外和体内的重要性也被认为是 获得。

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.