Mechanisms of differential responses to whole cell and acellular pertussis vaccination

全细胞和无细胞百日咳疫苗接种的差异反应机制

基本信息

批准号：
10585309
负责人：
Alessandro Sette
金额：
$ 80.82万
依托单位：
LA JOLLA INSTITUTE FOR IMMUNOLOGY
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：
2019-03-11 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10585309
关键词：
Antibody Response Antibody-mediated protection Antigens B-Lymphocytes Bacteria Bacterial Infections Biology Biopsy Blood CD4 Positive T Lymphocytes Cells Cellular biology Characteristics Child Childhood Complex Data Disease Effector Cell Exhibits Fine needle aspiration biopsy Generations Heterogeneity Human Human Herpesvirus 4 Humoral Immunities Immune response Immunity Immunization Individual Infection Interleukin-9 Intervention Link Lung Lymphoid Tissue MHC Class II Genes Medical Memory Molecular Newborn Infant Pathologic Pertussis Pertussis Vaccine Phenotype Play Process Property Provider Recurrence Regulatory T-Lymphocyte Reporting Role Source Streptococcus pyogenes Structure of germinal center of lymph node T cell response Techniques Teenagers Testing Tissues Tonsil Tonsillectomy Tonsillitis Transforming Growth Factor beta Vaccinated Vaccination Vaccines Virus Virus Diseases adaptive immune response cohort cost effective cytokine cytotoxic imprint in vivo individual response infancy innovation lymph nodes memory CD4 T lymphocyte novel pathogen polarized cell response single-cell RNA sequencing transcription factor vaccine development vaccine response

项目摘要

PROJECT SUMMARY Overall Component Vaccines are one of the most cost effective and extraordinarily successful medical interventions. Most of those vaccines depend on CD4 T+ cells and their help to B cells. Our understanding of in vivo, specific human CD4+ T cell responses to pathogens remains hazy, due to the complexity of the biology, the rarity of the cells, relatively inaccessible tissue localization, and technical challenges of identifying specific CD4+ T cells. Therefore, our approach to this serious problem has been to develop multiple new techniques to study human CD4+ T cells over the past several years. While CD4+ T cell-dependent antibody responses have been the source of protection for most licensed vaccines (Project 1), there is a very good argument to be made that many of the diseases for which we do not have successful vaccines require adaptive immune responses beyond antibodies for protection (Projects 2 and 3). The three Projects proposed here vigorously pursue an understanding of the mechanisms regulating human anti-pathogen CD4+ T cells, linked by new experimental approaches.

项目概要整体组成疫苗是最具成本效益且非常成功的医疗干预措施之一。其中大多数疫苗依赖于 CD4 T+ 细胞及其对 B 细胞的帮助。我们对体内特定人类 CD4+ T 的理解由于生物学的复杂性和细胞的稀有性，细胞对病原体的反应仍然模糊难以接近的组织定位以及识别特定 CD4+ T 细胞的技术挑战。因此，我们的解决这一严重问题的方法是开发多种新技术来研究人类 CD4+ T 细胞过去几年。虽然 CD4+ T 细胞依赖性抗体反应一直是保护的来源对于大多数获得许可的疫苗（项目 1），有一个很好的论据认为，许多疾病我们还没有成功的疫苗，需要抗体以外的适应性免疫反应来提供保护（项目 2 和 3）。这里提出的三个项目大力追求对机制的理解通过新的实验方法来调节人类抗病原体 CD4+ T 细胞。