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MHC class II immunopeptidomics analysis of the SARS-CoV-2 proteome

SARS-CoV-2 蛋白质组的 MHC II 类免疫肽组学分析

基本信息

批准号：
10491687
负责人：
Robert Lochhead
金额：
$ 19.5万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491687
关键词：
2019-nCoV Affinity Alleles Antibodies Antigen-Presenting Cells Antigens Award B-Lymphocytes Binding Blood donor Borrelia burgdorferi CD4 Positive T Lymphocytes COVID-19 COVID-19 vaccine Cells Complex Coronavirus Cytotoxic T-Lymphocytes Data Dendritic Cells Development Epidemic Epitopes Future HLA-DR Antigens Helper-Inducer T-Lymphocyte Hematopoietic stem cells Herd Immunity Histocompatibility Antigens Class II Human Immunity Immunization Immunize Immunoglobulin Class Switching Incubated Infection Lyme Disease MHC Class II Genes Membrane Proteins Memory Memory B-Lymphocyte Methods Nature Nucleocapsid Proteins Peptide/MHC Complex Peptides Peripheral Blood Mononuclear Cell Phagolysosome Proteins Proteome Public Health Publishing Recombinants Research Research Design Research Project Summaries SARS coronavirus SARS-CoV-2 immunity Sequence Homology Social Distance Source T cell response T-Lymphocyte T-Lymphocyte Epitopes Technology Testing Th1 Cells Time Vaccine Design Vaccines Viral Viral Antigens Viral Proteins Virus Virus Activation base cytotoxic CD8 T cells design env Gene Products humanized mouse immunogenic in silico innovation insight mouse model novel pandemic disease response tandem mass spectrometry

项目摘要

SUMMARY OF RESEARCH PROJECT COVID-19 is a global pandemic, the scope of which has not been seen in a century, and there is a critical unmet need for a vaccine to provide herd immunity against SARS-CoV-2. The objective of this proposal is to identify conserved immunodominant MHC class II peptides from the SARS-CoV-2 proteome that may be incorporated into current vaccine design studies. This meets a critical need to design a vaccine that will provide long-term protective immunity against COVID-19. This proposal uses an innovative immunopeptidomics platform to define the human SARS-CoV-2 MHC class II immunopeptidome using tandem mass spectrometry (Aim 1), and to determine CD4+ T cell responses to potentially immunogenic SARS-CoV-2 MHC-II peptides using a humanized mouse model (Aim 2). Robust CD4+ T cell responses to viral peptides are essential for establishing a pool of long-lived memory B cells and cytotoxic T cells. Results from this study will provide valuable insights into CD4+ T cell responses to viral proteins that may be rapidly incorporated into a vaccine design that will provide long-lasting protection from COVID-19.

研究项目总结新冠肺炎是一场全球性的流行病，其范围之广是百年未见的，而且有一个严重的未得到满足的需要一种疫苗来提供对SARS-CoV-2的群体免疫力。这项提案的目标是确定 SARS-CoV-2蛋白质组中可能被整合的保守的免疫优势MHC II类多肽到目前的疫苗设计研究中。这满足了设计一种长期有效的疫苗的迫切需要。对新冠肺炎的保护性免疫。这项提案使用创新的免疫营养学平台来定义人类SARS-CoV-2 MHC II类用串联质谱仪(AIM 1)检测免疫表位，并测定CD4+T细胞对使用人源化小鼠模型的潜在免疫原性SARS-CoV-2 MHC-II多肽(目标2)。强健的CD4+ T细胞对病毒多肽的反应对于建立长寿记忆B细胞池是必不可少的，并具有细胞毒性 T细胞。这项研究的结果将为了解CD4+T细胞对病毒蛋白的反应提供有价值的见解可能会迅速被纳入疫苗设计，提供针对新冠肺炎的长期保护。