MUCOSAL IMMUNITY TO SIV INFECTION & VACCINES

对 SIV 感染的粘膜免疫

• 批准号: 6247271
• 负责人: LAWRENCE A. WILSON
• 金额: $ 7.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-09 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247271
• 关键词: AIDS; Mammalia; Primates; animal tissue; biological products; communicable diseases; immunology; intestines; lymphatic system; vaccines; virus

The identification of immune responses that protect against mucosal invasion is of paramount importance in the development of a vaccine capable of blocking the sexual transmission of HIV. To this end, we have examined immune responses induced in gut-associated tissues in the macaque in response to transient infection with 2 molecular infectious clones of SIV and have correlated these responses with protection against intracolonic challenge with a high dose of the primary heterologous isolate, SIV/DeltaB670. Only 1 of 7 inoculated monkeys developed a disseminated infection. Of the remaining 6 animals, a transient infection was apparently induced in two, because, despite the inability to detect SIV or virus-specific immune responses in the peripheral blood, a high level of MHC class I restricted cytotoxic T lymphocyte (CTL) activity directed against viral env determinants was identified in the intestinal lamina propria. Six months post-exposure, these 7 animals and 4 naive controls were challenged intracolonically with SIV/DeltaB670. SIV/DeltaB670 sequences were successfully identified in peripheral blood mononuclear cells by 3 weeks postchallenge in all monkeys except the two monkeys with gut-associated CTL. The association of env-specific CTL with protection was further supported by its detection at 3 weeks postchallenge in the lamina propria of only those animals that were protected. These experiments provide the first direct evidence for a role for MHC class I restricted CTL in protection against mucosal exposure.

识别可预防的免疫反应 粘膜侵袭在肿瘤的发展中是至关重要的。 能够阻断艾滋病毒性传播的疫苗。 本 最后，我们检查了肠道相关的免疫反应， 组织中的猕猴响应短暂感染2 SIV的分子感染性克隆， 保护免受高剂量的 主要异源分离物，SIV/DeltaB 670。 仅1/7接种 猴子出现了扩散性感染 其余6 动物，显然在两个中引起了短暂的感染，因为， 尽管无法检测SIV或病毒特异性免疫反应， 在外周血中，高水平的MHC I类限制性抗原 针对病毒包膜的细胞毒性T淋巴细胞（CTL）活性 在肠固有层中鉴定了决定簇。 六 暴露后3个月，这7只动物和4只未处理对照动物 用SIV/DeltaB 670进行结肠内攻击。 SIV/DeltaB670 在外周血单个核细胞中成功鉴定了序列， 除两只猴外，所有猴中攻毒后3周的细胞 与肠道相关的CTL env特异性CTL与 保护作用进一步得到了3周时检测到的支持 攻毒后仅在那些 保护. 这些实验提供了第一个直接证据， MHC I类限制性CTL在粘膜保护中的作用 exposure.