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

研究项目概要 COVID-19是一场全球性大流行病，其范围在世纪内从未见过， 需要一种疫苗来提供对SARS-CoV-2的群体免疫。本建议的目的是确定 来自SARS-CoV-2蛋白质组的保守免疫显性MHCII类肽，其可以被掺入 目前的疫苗设计研究。这满足了设计一种疫苗的迫切需要， 对COVID-19的保护性免疫。 该提案使用创新的免疫肽组学平台来定义人SARS-CoV-2 MHC II类 免疫肽组使用串联质谱法（目的1），并确定CD 4 + T细胞对 潜在免疫原性SARS-CoV-2 MHC-II肽的人源化小鼠模型（Aim 2）。稳健的CD 4 + T细胞对病毒肽的应答对于建立长寿记忆B细胞库和细胞毒性T细胞是必不可少的。 T细胞。这项研究的结果将为CD 4 + T细胞对病毒蛋白的反应提供有价值的见解， 可能会迅速纳入疫苗设计中，从而提供对COVID-19的持久保护。

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.