TEMPORAL ANALYSIS OF IMMUNE RESPONSES AND PROTECTION INDUCED BY SIVDELTANEF

SIVDELTANEF 引起的免疫反应和保护的时间分析

• 批准号: 7715532
• 负责人: Roger H Reeves
• 金额: $ 12.98万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715532
• 关键词: Animals; CD8B1 gene; Computer Retrieval of Information on Scientific Projects Database; Data; Dose; Frequencies; Funding; Grant; Growth; Immune response; Immunity; Immunization; Infection; Institution; Intravenous; Plasma; Proteome; Research; Research Personnel; Resources; Source; Sterility; T-Lymphocyte; United States National Institutes of Health; Vaccinated; Viral Load result; Viremia; Week; enzyme linked immunospot assay; insight; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies have demonstrated that immunization with SIVdeltanef results in partial protection against IV challenge with SIVmac251 at 5 weeks after immunization but complete protection by 15 weeks. These results suggest that detailed analysis of the ontogeny of immune responses after infection with SIVdeltanef should offer insights into the mechanisms of protective immunity. We undertook a comprehensive analysis of the ontogeny of SIV-specific immune responses induced by SIVdeltanef and the correlation of these responses to protection against intravenous challenge with SIVmac239. Relatively high frequency SIV-specific T cell responses were detected as early as 2 weeks after SIVdeltanef infection. Longitudinal analysis demonstrated ELISPOT responses had decayed by approximately one-third 14 weeks after infection, with no apparent broadening of the cellular immune response. Challenge of these animals with an intravenous dose of SIVmac239 at 5 and 15 weeks after infection revealed apparently sterile protection in all animals, with no wild-type plasma viremia detectable and expected high viral loads in unvaccinated controls. Analysis of whole proteome ELISPOT responses and tetramer responses revealed no evidence of anamnestic CD8+ T cell responses in vaccinated animals following challenge at either 5 or 15 weeks. These data demonstrate that protection against homologous protection with SIVmac239 can occur as early as 5 weeks after SIVdeltanef infection and that the previously observed maturation of protection against SIVmac251 does not appear to correlate with quantitative changes in SIV-specific CD8+ T cell responses.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 先前的研究表明，SIVdeltanef 免疫可在免疫后 5 周对 SIVmac251 的 IV 攻击产生部分保护，但在 15 周时可实现完全保护。 这些结果表明，对 SIVdeltanef 感染后免疫反应个体发育的详细分析应该有助于深入了解保护性免疫机制。 我们对 SIVdeltanef 诱导的 SIV 特异性免疫反应的个体发育以及这些反应与 SIVmac239 静脉注射保护的相关性进行了全面分析。 早在 SIVdeltanef 感染后 2 周就检测到相对高频的 SIV 特异性 T 细胞反应。 纵向分析表明，感染后 14 周，ELISPOT 反应衰减了约三分之一，细胞免疫反应没有明显扩大。 感染后 5 周和 15 周对这些动物进行静脉注射 SIVmac239 的攻击，结果显示所有动物均具有明显的无菌保护，未检测到野生型血浆病毒血症，并且未接种疫苗的对照中预期病毒载量较高。 对整个蛋白质组 ELISPOT 反应和四聚体反应的分析表明，在 5 周或 15 周攻击后，接种疫苗的动物中没有记忆性 CD8+ T 细胞反应的证据。 这些数据表明，针对 SIVmac239 的同源保护最早可在 SIVdeltanef 感染后 5 周发生，并且先前观察到的针对 SIVmac251 的保护成熟似乎与 SIV 特异性 CD8+ T 细胞反应的数量变化无关。