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

• 批准号: 10366648
• 负责人: Alessandro Sette
• 金额: $ 15.47万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 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/10366648
• 关键词: Antibody Response; Antibody-mediated protection; Antigens; Antiviral Agents; 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

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.

项目总结