SIV CHALLENGE OF SHIV INOCULATED RHESUS MACAQUES

意义艾滋病毒是一种性传播疾病和疫苗 能够防止艾滋病毒的性传播，应引起粘膜 生殖道的免疫反应。 目的为了确定 阴道内注射后发生的短暂病毒血症和免疫反应 （IVAG）、静脉内（IV）或鼻内（IN）接种SHIV 89.6，可以提供保护免受IVAG SIV攻击，SIV 89.6 感染/暴露动物阴道内用SIVmac攻毒 239. 结果IVAG免疫3只，IN免疫4只， 4只动物和6只IV免疫动物中的3只保护免于SIV 239 挑战. 对这些动物免疫反应的详细研究 证明了保护发生，尽管没有 阴道分泌物中SIV特异性伊加。 保护措施显然 不需要存在对高度可变的 病毒包膜的区域。 保护只发生在 感染SHIV超过28周的动物 在SIV挑战之前。 这一结果清楚地表明， 免疫途径影响IVAG的保护水平 用致病性SIV攻击。 另外18只动物被 用SIV 89.6免疫（6个通过IVAG途径，6个通过IV途径，6个通过IN途径 路线）。 这些动物将通过IVAG接种进行攻毒， 第239章很快 未来的方向我们将继续监测 记录临床结果的差异。 我们 设计研究，以确定保护性免疫反应， SHIV免疫的动物。 我们将研制出疫苗， 当通过适当的药物给药时， 路线 关键词疫苗保护，粘膜免疫，SIV阴道 NIH赠款AI 35545和AI 44480出版物Lu， X，H. Kiyono，D. Lu，S. Kawabata，J. Torten，S. Srinivasan，P.J. 戴利，J.R. McGhee，T. Lehner，C. J.米勒. 靶向淋巴结 用完全灭活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 用SIVmac 251进行阴道激发。 艾滋病 12：1-10. 1998. 麦克切斯尼 医学博士，J. R.柯林斯，D. Lu、X. Lu，J. Torten，R. L.阿什利，M. W. 克洛伊德角J.米勒。 隐匿性全身感染和持续性 恒河猴SIV特异性CD 4 + T细胞免疫应答 阴道内接种SIV后出现短暂性病毒血症。 J. Virology 72：10029-10035，1998.

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.