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.

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