Memory CD8 T cell immunity to respiratory viral infections

描述（由申请人提供）：该项目的目标是解决与记忆CD8 T细胞介导的呼吸道病毒感染保护相关的基本知识空白。我们的目标是提供对呼吸道病毒感染免疫的细胞基础的机械实验见解，因此，我们将使用复杂的试剂和小鼠呼吸道病毒感染模型的范围。通过这种方式，我们期望确定记忆CD8 T细胞免疫对引起呼吸道感染的病毒的共同和病原体特异性方面。由于伦理原因，这些研究不能在人类身上进行；然而，我们预计我们的机制数据将为新一代疫苗的开发提供重要信息。此外，迄今为止，致力于开发可翻译的有效疫苗递送系统以诱导针对呼吸道病毒感染的记忆性CD8 T细胞反应的努力仍处于起步阶段。这项建议的长期目标是利用我们在记忆CD8 T细胞生物学方面的专业知识来确定对一系列呼吸道病毒具有最佳保护性免疫的特征。此外，我们将以新的初步数据为基础，评估可转化的方法（如鼻流感疫苗fluist），以启动CD8 T细胞反应，从而提高对呼吸道感染的高水平、亚型超越免疫。在本提案中，我们将以令人兴奋的初步数据为基础，通过以下具体目标来实现这些长期目标：确定记忆性CD8 T细胞免疫抵抗呼吸道病毒感染（包括IAV、RSV和MHV- 1）所需的强度和细胞相互作用。目标2。确定记忆性CD8 T细胞免疫对抗呼吸道病毒感染的最佳特性。目标3。开发新的翻译方法来产生记忆性CD8 T细胞，提供针对呼吸道病毒感染的最佳保护。

DESCRIPTION (provided by applicant): The goal of this project is to address basic knowledge gaps relating to memory CD8 T cell mediated protection against respiratory virus infections. Our goal is to provide mechanistic experimental insight into the cellular basis for immunity to respiratory virus infection and thus, we will employ the sophisticated reagents and range of respiratory virus infection models available in mice. In this way, we expect to identify both common and pathogen-specific aspects of memory CD8 T cell immunity against viruses that cause respiratory infection. These studies cannot be carried out in humans for ethical reasons; however, we anticipate that our mechanistic data will provide important information to inform new generation vaccine development. Additionally, to date, efforts devoted towards developing translatable efficient vaccine delivery systems to induce memory CD8 T cell responses against respiratory virus infections remain at their infancy. The long-term goal of this proposal is to utilize our expertise in memory CD8 T cell biology to identify characteristics that permit optimal protective immunity against a spectrum of respiratory viruses. In addition, we will build on novel preliminary data to evaluate translatable approaches (such as the nasal influenza vaccine, Flumist") to prime CD8 T cell responses that can be boosted to provide high level, subtype transcending immunity to respiratory infection. In this proposal, we will build on our exciting preliminary data to address these long-term goals through the following specific aims: Aim 1. Determine the magnitude and cellular interactions required for memory CD8 T cell immunity against a spectrum of respiratory viral infections including IAV, RSV and MHV- 1. Aim 2. Define the optimal characteristics for memory CD8 T cell immunity against a spectrum of respiratory viral infections. Aim 3. Develop novel translational approaches to generate memory CD8 T cells that provide optimal protection against respiratory viral infections.