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）：该项目的目的是解决与记忆CD8 T细胞介导的针对呼吸病毒感染的保护有关的基本知识差距。我们的目标是提供对呼吸病毒感染免疫的细胞基础的机械实验见解，因此，我们将采用小鼠可用的复杂试剂和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细胞免疫的常见和病原体特异性方面针对引起呼吸道感染的病毒。由于道德原因，这些研究不能在人类中进行。但是，我们预计我们的机械数据将提供重要的信息，以告知新一代疫苗开发。此外，迄今为止，致力于开发可翻译有效的疫苗输送系统来诱导记忆CD8 T细胞反应针对呼吸道病毒感染的记忆。该提案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针对各种呼吸道病毒的最佳保护性免疫的特征。此外，我们将基于新型的初步数据，以评估可翻译的方法（例如鼻流感疫苗，浮动剂，“ FLUMIST”），以促进CD8 T细胞反应，可以促进以高水平的超级超级超级呼吸的免疫力，以实现这一建议，在此提案中，我们将在我们的长期数据上构建一级的目标：在此提案中，我们将确定1次互动的目标：确定1个以下范围：确定1个范围的目标：确定1个以下方面的目标。记忆CD8 T细胞免疫对包括IAV，RSV和MHV-1的呼吸道病毒感染的范围。目标2。定义记忆CD8 T细胞免疫的最佳特征，以针对呼吸道病毒性感染的多种呼吸道感染。