Microarray Studies to Discover Novel Host Defenses in SIV Infection

微阵列研究发现 SIV 感染的新型宿主防御

• 批准号: 8069561
• 负责人: ASHLEY T. HAASE
• 金额: $ 18.69万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2012-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069561
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Africa; Animal Model; Animals; Attention; Attenuated; B-Lymphocytes; CD4 Positive T Lymphocytes; Cervical; Cessation of life; Development; Economics; Epithelial; Equilibrium; Future; Gene Expression; HIV-1; Host Defense; Human; Immune response; Infection; Inflammatory; Life; Light; Lymphoid Tissue; Macaca mulatta; Modeling; Natural Immunity; Pathogenesis; Prevention; Recruitment Activity; Risk; SIV; Systemic infection; T-Lymphocyte; Time; Tissues; Up-Regulation; Vaccinated; Vaccination; Vaccines; Vagina; Virus; Woman; Work; adaptive immunity; base; design; insight; microbicide; news; nonhuman primate; novel; prevent; prophylactic; public health relevance; response; transmission process; vaginal transmission

DESCRIPTION (provided by applicant): An effective vaccine is needed for prevention of HIV-1 transmission. This proposal is directed to identifying, in the SIV-rhesus macaque animal model, correlates of protection against vaginal transmission conferred by prior infection with an attenuated ?-nef strain of SIV. Microarray transcriptional profiling of cervical, vaginal and lymphatic tissues, at times when the extent of protection differs markedly, is proposed as a means to identify correlates of protection in: (i) particular or novel components of innate and adaptive immunity; (ii) a balanced up-regulation of innate and adaptive immune responses without the pro-inflammatory component that recruits CD4 T cells to fuel local expansion and systemic infection; and (iii) mechanisms of protection related to unexpected components of the innate and adaptive response, mechanisms related to the mucosal epithelial response to virus exposure, or wholly novel defenses suggested by the microarrays. These insights can then be harnessed in future work to design an effective vaccine to protect women from HIV-1 acquisition. PUBLIC HEALTH RELEVANCE: An effective vaccine to prevent HIV-1 is urgently needed. In this proposal, transcriptional profiles of cervical, vaginal and lymphatic tissues will be determined in infection with an attenuated ?-nef strain of SIV to identify novel correlates of protection with this vaccine approach.

描述（由申请人提供）：需要一种有效的疫苗来预防 HIV-1 传播。该提案旨在在 SIV-恒河猴动物模型中确定先前感染 SIV 减毒 α-nef 株所赋予的针对阴道传播的保护的相关性。当保护程度显着不同时，建议对宫颈、阴道和淋巴组织进行微阵列转录分析，作为识别以下方面保护相关性的一种手段：(i) 先天性和适应性免疫的特定或新成分； (ii) 先天性和适应性免疫反应的平衡上调，无需募集 CD4 T 细胞以促进局部扩张和全身感染的促炎成分； (iii) 与先天性和适应性反应的意外成分相关的保护机制、与病毒暴露的粘膜上皮反应相关的机制、或微阵列建议的全新防御机制。然后可以在未来的工作中利用这些见解来设计一种有效的疫苗，以保护女性免受 HIV-1 感染。 公共卫生相关性：迫切需要一种有效的疫苗来预防 HIV-1。在该提案中，将确定 SIV α-nef 减毒株感染时宫颈、阴道和淋巴组织的转录谱，以确定与该疫苗方法的新的保护相关性。