HIV-specific responses mediated by human NK cells

由人类 NK 细胞介导的 HIV 特异性反应

• 批准号: 8991710
• 负责人: Stephanie Jost
• 金额: $ 43.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-05 至 2016-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8991710
• 关键词: Acute; Address; Antigens; Antiviral Agents; B-Lymphocytes; Cells; Communicable Diseases; Data; Disease Progression; Effector Cell; Epidemiologic Studies; Failure; Future; HIV; HIV-1; HIV-1 vaccine; Haptens; Health; Human; Human Characteristics; Immune; Immune system; Immunity; Immunization; Immunoglobulins; Immunologic Memory; In Vitro; Individual; Infection; Investigation; Killer Cells; Laboratories; Lead; Life; Ligands; Liver; Mediating; Memory; Mucous Membrane; Mus; Natural Killer Cells; Outcome; Population; Property; Prophylactic treatment; Receptor Gene; Reporting; Research Design; Serotyping; Spleen; T-Lymphocyte; Testing; Time; Vaccine Design; Vaccines; Viral; Viral Antigens; Virus; Virus Diseases; arm; design; improved; in vivo; innovation; mouse model; mucosal site; nonhuman primate; novel; novel strategies; pathogen; peripheral blood; pressure; prevent; protective effect; recombinant adenovirus; response; success; trafficking; transmission process; vaccine candidate

 DESCRIPTION (provided by applicant): The failure or modest success of previous vaccine approaches to protect from HIV-1 infection have highlighted that our understanding of protective immunity in HIV-1 infection is very limited, and that novel, innovative strategies are needed to overcome the tremendous challenges we are facing in HIV-1 vaccine design. NK cells represent important early effector cells against viral infections, and increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans. While the ability of NK cells to eliminate infected cells has long been recognized, recent studies conducted in mouse models revealed a subset of murine NK cells that can acquire specific long-lived memory of multiple haptens and viral antigens, including HIV-1 antigens. These exciting data suggest that a subset of NK cells in humans may also mediate immunological memory responses to pathogens in humans, and that NK cell responses may significantly contribute to the protective effect mediated by HIV-1 vaccines. Therefore, we propose to comprehensively explore HIV-1-specific NK cell responses in HIV-1-infected subjects and in HIV-1-negative individuals following immunization with HIV-1 vaccines, including vaccines that are currently being tested in humans. The results of these innovative explorative studies could provide the rationale to harness antigen-specific NK cell responses to enhance the potency of HIV-1 vaccines and to improve the design of vaccines to prevent other infectious diseases for which there is currently no available or effective enough prophylaxis.

 描述（由申请人提供）：先前预防HIV-1感染的疫苗方法的失败或适度成功突出表明，我们对HIV-1感染的保护性免疫的理解非常有限，需要新颖的创新策略来克服我们在HIV-1疫苗设计中面临的巨大挑战。NK细胞是对抗病毒感染的重要早期效应细胞，越来越多的数据表明NK细胞可以介导HIV-1感染者的抗病毒活性。虽然NK细胞清除 感染细胞的免疫应答早已被认识到，最近在小鼠模型中进行的研究揭示了鼠NK细胞的一个亚群，其可以获得多种半抗原和病毒抗原（包括HIV-1抗原）的特异性长寿命记忆。这些令人兴奋的数据表明，人类NK细胞的一个子集也可能介导对人类病原体的免疫记忆反应，并且NK细胞反应可能显著有助于HIV-1疫苗介导的保护作用。因此，我们建议全面探索HIV-1感染受试者和HIV-1阴性个体在接种HIV-1疫苗（包括目前正在人体中测试的疫苗）后的HIV-1特异性NK细胞应答。这些创新的探索性研究的结果可以提供利用抗原特异性NK细胞应答来增强HIV-1疫苗的效力和改进疫苗设计以预防目前没有可用或有效预防的其他传染病的理论基础。