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High-Throughput TB Vaccine Antigen Discovery

高通量结核疫苗抗原发现

基本信息

批准号：
10468128
负责人：
Amanda Martinot
金额：
$ 15.85万
依托单位：
TUFTS UNIVERSITY BOSTON
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：
2019-06-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468128
关键词：
Adenovirus Vector Adult Animal Model Animals Antigens Antitubercular Agents BCG Live Bacille Calmette-Guerin vaccination Bacteriology Bar Codes CD8-Positive T-Lymphocytes Cells Child Childhood Clinical Trials Communicable Diseases Coupled DNA Vaccines Data Development Disease Expression Library Failure Gene Library Genes Genome Goals Growth HIV HIV vaccine Head Immune Immune response Immunity Immunodominant Antigens Immunology Infection Interferon Type II Israel Knowledge Laboratories Libraries Lymphocyte antigen Medical center Meningeal Tuberculosis Mentorship Microbiology Modeling Mucous Membrane Mus Open Reading Frames Persons Population Positioning Attribute Proteins Proteome Pulmonary Tuberculosis Research Research Personnel Surface T cell response T memory cell T-Lymphocyte Testing Training Tuberculosis Tuberculosis Vaccines Vaccine Antigen Vaccine Design Vaccine Research Vaccines Whole Cell Vaccine Work ZIKV infection deep sequencing design genome-wide immunogenic immunogenicity immunopathology in vivo innovation mouse model mycobacterial new technology novel novel vaccines prevent primary endpoint protective efficacy response skills translational medicine vaccination against tuberculosis vaccine candidate vaccine development vaccine discovery vaccine efficacy vaccine strategy vaccinology virology

项目摘要

Project Summary/Abstract: Approximately one third of the world's population is infected with latent tuberculosis (LTBI). While BCG vaccination protects some children against pediatric tuberculous meningitis, it does not prevent the most prevalent form of disease, pulmonary TB disease in adults. To date, every new tuberculosis (TB) vaccine candidate has failed in large-scale clinical trials and no known immune correlates of vaccine protection for TB have been validated. Failure of new TB vaccines such as MVA-85A, despite generating high-magnitude Th1 immune responses against the immunodominant antigen, Ag85A, is likely related to the exclusive use of immunodominant antigens in these vaccines, despite poor correlation of immunodominant responses with vaccine efficacy. These facts highlight a critical need for discovery of novel subdominant TB antigens for use in TB vaccines that can enhance functional immunity and bacterial killing. Here we propose a novel TB antigen discovery platform that enables systematic and unbiased probing of a TB genome-wide DNA vaccine library with the overall objective to identify new TB antigens. Our specific aims are to generate immune responses to pooled subdominant antigens in mice and to identify novel subdominant immunogens with capacity to induce protective immunity. We aim to do this by in vivo interrogation of the TB proteome using the mouse challenge model. Our long-term goal is to inform TB vaccine design and to uncover novel immune correlates of vaccine protection for TB. Achieving these aims has the capacity to transform the TB vaccine field and contribute to the development of an efficacious TB vaccine. The Barouch laboratory at Beth Israel Deaconess Medical Center leads in vaccine design and discovery for diseases such as HIV and Zika virus infection. I aim to synergize my expertise in TB bacteriology and animal models with enhanced training in immunology and vaccinology at the Center for Virology and Vaccine Research to gain the skills necessary to position myself to become a leader in TB vaccine discovery as a principle investigator and head of my own research group.

项目总结/文摘: