权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Maintaining Robust T Cell Immunity For Broad Protection Against Influenza

维持强大的 T 细胞免疫力以广泛预防流感

基本信息

批准号：
9806329
负责人：
SUSAN L SWAIN
金额：
$ 25.13万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-18 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9806329
关键词：
Adjuvant Adult Affinity Antibodies Antibody Formation Antibody titer measurement Antigen Presentation Antigens Antiviral Agents Attenuated Automobile Driving B-Lymphocytes CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Capsid Proteins Cells Cellular Immunity Cessation of life Childhood Consensus Core Protein Death Rate Development Disease Disease Outbreaks Dose Epitopes Exposure to FluMist Generations Health Hazards Human Immunity In Situ In Vitro Inactivated Vaccines Individual Infection Infection prevention Influenza Influenza A virus Life Lung Mediating Membrane Glycoproteins Memory Memory B-Lymphocyte Molecular Mus Mutate Natural regeneration Oils Pattern Peptides Persons Secondary to Signal Transduction Symptoms T cell response T memory cell T-Lymphocyte Time Vaccination Vaccines Variant Viral Antigens Virus Virus Diseases Water Work aging population bone cell injury cytokine cytotoxic design in vivo in vivo evaluation influenza virus vaccine influenzavirus memory CD4 T lymphocyte neutralizing antibody pandemic disease pathogen prevent repaired response universal vaccine

项目摘要

ABSTRACT: Maintaining Robust T Cell Immunity for Broad Protection Against Influenza Influenza vaccines currently in use are designed, primarily to produce neutralizing antibody to coat proteins and must be reformulated and given each year. They are only partially effective, while live infection confers highly protective T cell mediated immunity which provides multiple additional protective mechanisms and also is crucial for generation of long-lasting neutralizing Ab. Our recent studies indicate that generation of protective CD4 T cell immunity requires strong presentation of viral antigen and infection-mediated signals lasting at least a week. This is because the effectors need to receive these signals during a clear-cut checkpoint to complete their transition to memory. Current vaccines rarely supply Ag or the relevant pathogen-recognition signals (PRS) at optimal levels for this long. Moreover, human responses often depend on already generated memory T cells, and it is not known whether memory CD4 T cells must go through a similar checkpoint to re-generate secondary (20) memory responses. Here we will compare the in vivo 20 response of memory CD4 T cells generated by inactivated whole influenza vaccine vs. live infection and determine whether the 20 CD4 effectors also need Ag and pathogen signals at a comparable “effector checkpoint”, via similar mechanisms, to re-generate 20 CD4 memory and if such memory does indeed provide strong heterosubtypic protection against multiple influenza A viruses. If so, it should be possible to augment vaccines to provide the Ag and pathogen signals both initially and at the checkpoint, and this should create a framework for a new generation of more effective vaccines against influenza that are more broadly protective and give long-lasting immunity. Moreover, it is likely that the same strategies could be applied to vaccines against other pathogens.

摘要：维持强大的T细胞免疫对流感的广泛保护