HIV-specific responses mediated by human NK cells

 描述(由申请人提供)：以前预防艾滋病毒-1感染的疫苗方法的失败或适度成功，突显了我们对艾滋病毒-1感染的保护性免疫的了解非常有限，需要新颖、创新的战略来克服我们在艾滋病毒-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，在HIV-1感染者中，NK细胞可以介导抗病毒活性。而NK细胞清除的能力 被感染的细胞早已被识别，最近在小鼠模型中进行的研究揭示了小鼠NK细胞的一个亚群，它可以获得对多个半抗原和病毒抗原(包括HIV-1抗原)的特定的长期记忆。这些令人兴奋的数据表明，人类中的NK细胞亚群也可能介导人类对病原体的免疫记忆反应，并且NK细胞反应可能对HIV-1疫苗介导的保护作用做出重大贡献。因此，我们建议全面探索HIV-1感染者和HIV-1阴性个体在接种HIV-1疫苗后的HIV-1特异性NK细胞反应，包括目前正在人类身上测试的疫苗。这些创新性的探索性研究结果可能为利用抗原特异性NK细胞反应来提高HIV-1疫苗的效力以及改进疫苗设计以预防其他目前尚无或有效预防的其他传染病提供了理论基础。

 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.