Cellular Immunity and Memory to SARS-CoV-2

项目2摘要 项目2的目标是更好地表征SARS-CoV-2的细胞免疫和记忆。这个项目 将通过定义细胞免疫的相关性来补充项目1，包括CD 4 T细胞、CD 8 T细胞和B- 细胞记忆，这可能比血清学反应更持久。与项目1一样，项目2将使用 从临床队列核心和免疫分析开发的许多检测中收集的样本 核心独特的是，因为我们的临床队列包括儿科和成人受试者， （35-50%），以及癌症队列，我们将能够测试一些不同的免疫反应差异。 人口。在研究期间，我们将完成以下目标：（1）定义细胞反应 建立后SARS-CoV-2感染和人类受试者队列之间的差异。CD 4+和CD 8 + T- 在用SARS-CoV-2 S、N和M肽刺激后测定细胞活化，并与 抗体分泌细胞。我们还将研究这些反应中的任何一种是否在小鼠COVID-19中重现 模型(2)确定对SARS-CoV-2的单个T细胞表位的应答，以及MHC-II单倍型是否 与“不稳定”的T细胞表位相关，因此B细胞反应较弱。(3)确定SARS的持续性- CoV-2记忆反应和人类受试者队列之间的差异。这包括对蜂窝网络的更改 和血清免疫力。通过分析呼吸道和唾液中的粘膜反应， 和粪便中，我们还将评估粘膜免疫与外周血反应。(4)定义 SARS-CoV-2暴露与对其他病原体的免疫记忆之间的关系。我们将比较 对其他病毒的血清学反应，包括季节性冠状病毒、流感、脊髓灰质炎和MMR 在当前大流行之前和爆发之后收集的样本中，如果SARS- CoV-2感染改变了对其他病原体或疫苗的免疫力。所有研究将使用样本进行 从整个生命周期的队列中，以及那些有和没有癌症诊断的人群中。完成时 在提案期间，上述目标将导致我们对T细胞的理解取得重大进展， B细胞对SARS-CoV-2的记忆以及与项目1中血清学评价的关系。这些进步是 这对我们理解SARS-CoV-2的血清学反应以及最终理解 对病毒感染的保护性免疫甚至是接种疫苗。

Project 2 Summary The goal of Project 2 is to better characterize the cellular immunity and memory to SARS-CoV-2. This project will complement Project 1 by defining correlates of cellular immunity, including CD4 T-cell, CD8 T-cell, and B- cell memory, which may be longer lasting than serological responses. Like Project 1, Project 2 will use samples collected from the Clinical Cohort Core and many of the assays developed by the ImmunoAssay Core. Uniquely, because our clinical cohorts include pediatric and adult subjects, large numbers of minorities (35-50%), and a cancer cohort, we will be able to test for immune response differences in a number of distinct populations. During the proposal period, we will complete the following aims: (1) Define the cellular responses established after SARS-CoV-2 infection and differences between human subject cohorts. CD4+ and CD8+ T- cell activation will be determined after stimulation with SARS-CoV-2 S, N and M peptides and compared to antibody-secreting cells. We will also examine if any of these responses are recapitulated in mouse COVID-19 models. (2) Identify responses to individual T-cell epitopes of SARS-CoV-2 and whether MHC-II haplotypes are associated with ‘unstable’ T-cell epitopes, and thus weak B-cell responses. (3) Identify persistence of SARS- CoV-2 memory responses and differences between human subject cohorts. This includes changes to cellular and serological immunity over time. By assaying mucosal responses in the respiratory tract, as well as saliva and feces, we will also evaluate mucosal immunity versus peripheral blood responses. (4) Define the relationship between SARS-CoV-2 exposure and immunologic memory to other pathogens. We will compare the serological response to other viruses including seasonal coronaviruses, influenza, polio and MMR as well as tetanus toxoid in samples collected before the current pandemic and after its onset. Identifying if SARS- CoV-2 infection alters immunity to other pathogens or vaccines. All studies will be performed using samples from cohorts across the lifespan and among those with and without a cancer diagnosis. At the completion of the proposal period, the aims described above will result in a major advance in our understanding of T-cell and B-cell memory to SARS-CoV-2 and relationship to serological evaluation in Project 1. Such advancements are critical to our understanding of the serological response to SARS-CoV-2 as well as the ultimate understanding of protective immunity to viral infection or even vaccination.