SIV CHALLENGE OF SHIV INOCULATED RHESUS MACAQUES

意义艾滋病毒是一种性传播疾病和疫苗 能够防止性传播艾滋病毒的人应该引起粘膜 生殖道中的免疫反应。目标，以确定是否 阴道内注射后发生的一过性病毒血症和免疫反应 静脉接种(IVAG)、静脉接种(IV)或鼻腔接种(IN) 89.6，可以提供针对IVAG SIV挑战的保护，Shiv 89.6 感染/暴露的动物经阴道感染SIVmac 239.结果3只IVAG免疫动物中3只免疫，6只免疫动物中4只免疫 动物和6只IV免疫动物中的3只免受SIV239感染 挑战。对这些动物的免疫反应的详细研究 证明这种保护是在没有 阴道分泌物中的SIV特异性IgA。保护措施显然起到了作用。 不需要存在高度可变的免疫反应 病毒包膜的区域。这种保护只发生在 感染新城疫病毒超过28周的动物 在SIV挑战赛之前。这一结果清楚地表明， 免疫途径影响对IVAG的保护水平 挑战致病性SIV。另外18只动物已经被 SIV 89.6疫苗(静脉注射免疫6例，静脉注射免疫6例，静脉注射免疫6例 路线)。这些动物将通过IVAG接种来挑战 西夫马克239号快要到了。未来的发展方向我们将继续关注 这些动物记录临床结果的差异。我们是 设计研究以确定儿童的保护性免疫反应 希沃氏病毒免疫的动物。然后我们将开发出能够 当给药时引起相似的免疫反应 路线。关键词疫苗保护、粘膜免疫、SIV阴道 美国国立卫生研究院传播基金资助AI35545和AI44480出版物鲁， 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 书名/作者声明：[by]J.靶向淋巴结 全灭活SIV或包膜和核心亚单位免疫 抗原疫苗不能可靠地保护恒河猴免受 使用SIVmac251进行阴道挑战。艾滋病。12：1-10。1998年。麦克切斯尼 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 克洛伊德·C·J·米勒隐性全身性感染与持续性 恒河猴体内SIV特异性的CD4T细胞增殖反应 经阴道接种SIV后出现一过性病毒感染。 《病毒学》72：10029-10035,1998年。

Significance HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. Objectives To determine if the transient viremia and immune response that occurs after intravaginal (IVAG), intravenous (IV) or intranasal (IN) inoculation with SHIV 89.6, could confer protection from IVAG SIV challenge, the SHIV 89.6 infected/exposed animals were challenged intravaginally with SIVmac 239. Results Three of 3 IVAG immunized animals, 4 of 6 IN immunized animals and 3 of 6 IV immunized animals were protected from SIV239 challenge. Detailed studies of the immune responses in these animals demonstrated that the protection occurs despite the absence of SIV-specific IgA in vaginal secretions. The protection apparently did not require the presence of immune responses to highly variable regions of the viral envelope. The protection occurred only in animals that had been infected with the SHIV for more than 28 weeks before the SIV challenge. This result clearly demonstrates that the route of immunization effects the level of protection from IVAG challenge with pathogenic SIV. Eighteen additional animals have been immunized with SHIV 89.6 (6 by IVAG route, 6 by IV route and 6 by IN route). These animals will be challenged by IVAG inoculation with SIVmac 239 shortly. Future Directions We are continuing to monitor the animals to document differences in clinical outcome. We are designing studies to identify the protective immune responses in the SHIV-immunized animals. We will then develop vaccines which can elicit similar immune responses when administered by the appropriate route. KEY WORDS vaccine protection, mucosal immunity, SIV vaginal transmission FUNDING NIH Grants AI35545 and AI44480 PUBLICATIONS Lu, X, H. Kiyono, D. Lu, S. Kawabata, J. Torten, S. Srinivasan, P.J. Dailey, J.R. McGhee, T. Lehner, C.J. Miller. Targeted lymph node immunization with whole-inactivated SIV or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIVmac251. AIDS. 12:1-10. 1998. McChesney M.B., J. R. Collins, D. Lu, X. Lu, J. Torten, R. L. Ashley, M. W. Cloyd, C. J. Miller. Occult Systemic Infection and Persistent SIV-Specific CD4+ T Cell Proliferative Responses in Rhesus Macaques that Were Transiently Viremic after Intravaginal Inoculation of SIV. J. Virology 72:10029-10035, 1998.