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Antiviral lung resident memory T cell maintenance and reinvigoration

抗病毒肺驻留记忆 T 细胞的维持和重振

基本信息

批准号：
10603176
负责人：
Mariah A Hassert
金额：
$ 6.91万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10603176
关键词：
2019-nCoV Address Antibodies Antigen-Presenting Cells Antigens Benchmarking Biology CD8-Positive T-Lymphocytes Cell Maintenance Cell Separation Cells Cellular biology Cessation of life Development Epitopes Exposure to Formulation Generations Genes Goals Health Hemagglutinin Hospitalization Human Humoral Immunities Immunity Immunization Immunologics Inactivated Vaccines Infection Influenza Influenza A virus Intramuscular Intrinsic factor Knowledge Longevity Lung Maintenance Mediating Memory Messenger RNA Metabolic Molecular Neuraminidase Peripheral Play Population Public Health RNA vaccine Recurrence Role Route Seasons Skin Spleen Structure of parenchyma of lung Surface Antigens T memory cell T-Lymphocyte Testing Time Tissues Transcend Transforming Growth Factor beta Vaccination Vaccines Viral Viral Respiratory Tract Infection cell type clinically relevant cross immunity cross reactivity cytokine design differential expression fatty acid metabolism influenza virus vaccine innovation intestinal epithelium lipid nanoparticle metabolic abnormality assessment migration mouse model neutralizing antibody novel pandemic influenza pandemic potential pathogen pathogenic virus rational design respiratory virus seasonal influenza success tissue resident memory T cell transcriptomics universal influenza vaccine vaccination strategy vaccine access vaccine platform

项目摘要

PROJECT SUMMARY Seasonal influenza A (IAV) and other airborne viral pathogens such as SARS-CoV-2 represent a substantial burden on global public health. While sterilizing immunity can be attained through neutralizing antibodies, seasonal antigenic drift permits viral evasion of humoral immunity, which necessitates annual reformulation of the seasonal influenza vaccine. It has previously been shown, that cross-reactive CD8+ T cells can provide heterosubtypic non-sterilizing immunity to IAV. However, this cross-protection is relatively short-lived in the context of a singular antigen exposure. Our lab has shown that lung tissue resident memory T cells (lung Trm) contribute to this strain transcending cross-protection and that the waning in numbers of IAV-specific Trm strongly correlate with this loss of IAV cross-protection. Importantly, we have found that multiple exposures to the same IAV antigens (boosting) can extend the longevity of these lung Trm populations, and as a result, provide extended heterosubtypic immunity. There still exists a substantial knowledge gap regarding why lung Trm cells are so short lived when they are clearly important for protection. Addressing this question remains a critical step in the rational design of universal influenza vaccines. Our long-term goal is to understand the biology that underlies the waning of lung Trm cells and to harness this information to aid in the development of broadly protective influenza vaccines. We will address this long-term goal with the following specific aims: Aim 1: Determine the molecular T cell intrinsic factors that permit extended longevity and functionality of lung Trm following multiple antigen exposures. Aim 2: Define the optimal priming and boosting vaccination strategies to maximize Trm generation, re- invigoration, and function.

项目总结