Memory CD8 T cell immunity to respiratory viral infections

记忆 CD8 T 细胞对呼吸道病毒感染的免疫

• 批准号: 8699313
• 负责人: John T Harty
• 金额: $ 35.49万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699313
• 关键词: Address; Antibodies; Area; Biology; CD8B1 gene; Cells; Cellular biology; Characteristics; Coronavirus; Data; Development; Disease; Ethics; Flushield; Generations; Goals; Health; Human; Immunity; Infection; Influenza A virus; Knowledge; Lung; Lung diseases; Mediating; Memory; Modeling; Morbidity - disease rate; Murine hepatitis virus; Mus; Nose; Physiology; Play; Primates; Principal Investigator; Proteins; Reagent; Regulatory T-Lymphocyte; Resistance; Respiratory Tract Diseases; Respiratory Tract Infections; Respiratory syncytial virus; Role; Sendai virus; Symptoms; System; T cell response; T memory cell; T-Lymphocyte; Transcend; Vaccinated; Vaccines; Viral; Virus; Virus Diseases; Work; base; experience; immunopathology; improved; infancy; influenza virus vaccine; influenzavirus; insight; mortality; neutralizing antibody; novel; pathogen; programs; respiratory; respiratory infection virus; respiratory virus; seasonal influenza; translational approach; vaccine delivery; vaccine development

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.

描述(由申请人提供)：这个项目的目标是解决与记忆CD8 T细胞介导的预防呼吸道病毒感染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学基础的机械性实验洞察，因此，我们将使用先进的试剂和一系列在小鼠身上可用的呼吸道病毒感染模型。通过这种方式，我们希望识别记忆CD8 T细胞免疫的共同和病原体特异性方面，以对抗导致呼吸道感染的病毒。由于伦理原因，这些研究不能在人类身上进行；然而，我们预计我们的机械数据将提供重要信息，为新一代疫苗的开发提供信息。此外，迄今为止，致力于开发可翻译的高效疫苗递送系统以诱导针对呼吸道病毒感染的记忆CD8 T细胞反应的努力仍处于初级阶段。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允许对一系列呼吸道病毒产生最佳保护性免疫的特征。此外，我们将基于新的初步数据来评估可翻译的方法(如鼻流感疫苗，Flumist“)，以启动CD8 T细胞反应，这些反应可以增强，以提供对呼吸道感染的高水平、亚型以上的免疫。在这项提案中，我们将以我们令人兴奋的初步数据为基础，通过以下具体目标来解决这些长期目标：目标1.确定针对包括IAV、RSV和MHV-1在内的一系列呼吸道病毒感染的记忆CD8 T细胞免疫所需的大小和细胞相互作用。目标2.确定针对一系列呼吸道病毒感染的记忆CD8 T细胞免疫的最佳特征。目的3.开发新的翻译方法来产生记忆CD8 T细胞，以提供对呼吸道病毒感染的最佳保护。