NONINFECTIOUS SIV AS VACCINE MODEL

非感染性 SIV 作为疫苗模型

• 批准号: 6592294
• 负责人: SCOTT W WONG
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592294
• 关键词: AIDS; Mammalia; animal tissue; communicable diseases; hematology; immunology; inflammation; lymphatic system; model design /development; nervous system; vaccines; virus

Live attenuated simian immunodeficiency virus (SIV) has been shown to be the best candidate vaccine for inhibiting SIV infection. However, the ability of live attenuated SIV to cause AIDS-like disease in newborn macaques raises concern over the safety of a live virus as a vaccine. Thus, in an effort to improve on the live attenuated SIV as a vaccine, we generated a SIVmac239 construct which encodes sequence elements that should facilitate the excision of an integrated SIV proviral genome. In the previous year, we evaluated the ability of this recombinant SIVmac239 construct to replicate in transformed CD4+ T cells and in macaque peripheral blood mononuclear cells (PBMCs). From these in vitro studies we concluded that the recombinant SIVmac239 containing loxP sequence elements and the cre-recombinase gene is capable of replication in both cultured T cells and in primary rhesus PBMCs. This last year, we identified a group of six rhesus macaques for SIV-infection studies. PBMCs were isolated from these animals, infected in vitro with SIVmac239 and analyzed for virus production. From these studies we found that their PBMCs can support SIVmac239 infection and replication, as culture supernatants from these infected cell cultures produced SIV p27 antigen in the supernatant. The identification of animals susceptible to SIV infection is important for these studies, as animals that are resistant to SIV infection would complicate the interpretation of the data. Extensive evaluation of unique live attenuated SIV in rhesus macaques may provide the means for creating a safe and effective vaccine to prevent the progression of AIDS. FUNDING NIH RR00163 (Project 6) PUBLICATIONS None

已经显示了活体减弱的猿猴免疫缺陷病毒（SIV） 成为抑制SIV感染的最佳候选疫苗。 但是，活着衰减的SIV引起类似艾滋病的疾病的能力 在新生儿猕猴中，人们担心活病毒的安全性 疫苗。 因此，为了改善现场衰减的SIV 作为疫苗，我们生成了一个编码的SIVMAC239构造 序列元素应促进综合的切除 SIV病毒基因组。 在上一年，我们评估了能力 该重组SIVMAC239构建体以在变换中复制 CD4+ T细胞和猕猴外周血单核细胞 （PBMC）。 从这些体外研究中，我们得出的结论是 重组SIVMAC239包含LOXP序列元素和 Cre-recombinase基因在两个培养的T中都可以复制 细胞和原发性PBMC。 去年，我们确定了 用于SIV感染研究的六个恒河猕猴。 PBMC是 从这些动物中分离出来，在体外被SIVMAC239和 分析了病毒生产。 从这些研究中，我们发现他们 PBMC可以支持SIVMAC239感染和复制，作为培养 这些感染细胞培养物的上清液产生了SIV P27 上清液中的抗原。 识别动物易感的 对SIV感染对于这些研究很重要，因为 对SIV感染具有抗药性会使解释的解释复杂化 数据。 广泛评估恒河所中独特的现场衰减SIV 猕猴可能会提供创造安全有效的手段 防止艾滋病进展的疫苗。 资助NIH RR00163 （项目6）出版物无