IMMUNIZATION ACTIVATES TRANSIENT SIV VIRAL REPLICATION

免疫激活短暂的 SIV 病毒复制

• 批准号: 8358149
• 负责人: DREW WEISSMAN
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358149
• 关键词: Animals; Anti-Retroviral Agents; Antigens; CD4 Positive T Lymphocytes; Chronic; Contralateral; Cytomegalovirus; Funding; Gagging; Generations; Grant; HIV; HIV Antigens; HIV Infections; Immune; Immunity; Immunization; Individual; Infection; Institution; Macaca; Macaca mulatta; Modeling; National Center for Research Resources; Plasmids; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Side; Source; T cell response; Therapeutic; Time; United States National Institutes of Health; Viral; cost; cytomegalovirus matrix protein 65kDa; immune activation; lymph nodes; pathogen; peripheral blood; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many common pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected ART treated subjects results in poor HIV-specific responses. In this study, we used a macaque model of HIV-infected individuals treated with ART during chronic infection to study the consequences of SIV antigen stimulation in lymph nodes early after immunization. CMV seropositive Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and CMV pp65 antigen immunization in draining lymph nodes and peripheral blood was analyzed. Animals were immunized with SIV gag encoding plasmid on one side and CMV pp65 encoding plasmid on the contralateral side, which allowed draining lymph nodes for each antigen to be obtained at the same time from the same animal for direct comparison. We observed that both SIV and CMV antigen immunizations stimulated immune activation and transient antigen-specific T cell responses in inpsilateral lymph nodes. The CMV-specific responses were potent and sustained in the periphery for 50 days post-immunization, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation induced transient SIV viral replication in the draining lymph nodes. We hypothesize that viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses, suggesting a mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 HIV感染会导致CD4+ T细胞免疫的定性和定量损失。抗逆转录病毒疗法（ART）的制度恢复了CD4+ T细胞对许多常见病原体的反应，但HIV特异性反应仍然缺乏。同样，用慢性感染ART治疗的受试者的HIV抗原治疗免疫导致HIV特异性反应不良。在这项研究中，我们使用了在慢性感染期间接受ART治疗的HIV感染个体的猕猴模型，以研究免疫后早期淋巴结中SIV抗原刺激的后果。 CMV血清阳性Mamu A*01阳性猕猴长期感染SIVMAC251并用ART治疗。分析了对淋巴结和外周血中SIV GAG和CMV PP65抗原免疫的免疫反应。用SIV GAG对动物进行免疫，一侧编码质粒，CMV PP65编码对侧侧的质粒，从而使每种抗原的排水淋巴结从同一动物同时获得直接比较。我们观察到SIV和CMV抗原免疫均刺激了内侧淋巴结中的免疫激活和瞬时抗原特异性T细胞反应。免疫后50天，CMV特异性反应在外围持续50天，而SIV特异性响应是短暂的，并迅速熄灭。 SIV抗原刺激在排水淋巴结中引起的瞬态SIV病毒复制。我们假设对SIV抗原刺激的病毒复制限制了SIV抗原特异性反应的产生，这表明在HIV感染的个体中观察到的早期丧失和HIV特异性CD4+ T细胞反应的机制。