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因素来补充项目1，包括CD4T细胞、CD8T细胞和B细胞- 细胞记忆，这可能比血清学反应持续时间更长。与项目1类似，项目2将使用 从临床队列核心收集的样本和通过免疫分析开发的许多分析方法 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，大量的少数族裔 (35-50%)，与癌症队列相比，我们将能够测试免疫反应的差异在一些明显 人口。在提案期间，我们将完成以下目标：(1)定义细胞响应 建立了SARS-CoV-2感染后与人类受试者队列之间的差异。CD4+和CD8+T- 用SARS-CoV-2 S、N和M肽刺激细胞后测定细胞活性，并与 抗体分泌细胞。我们还将检查是否有任何这些反应在小鼠新冠肺炎中被概括 模特们。(2)确定对SARS-CoV-2单个T细胞表位的反应以及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)识别SARS的持久性- 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 以及随着时间推移的血清免疫力。通过分析呼吸道和唾液中的粘膜反应 和粪便，我们还将评估黏膜免疫和外周血液反应。(4)界定 SARS-CoV-2暴露与免疫记忆的关系我们会比较一下 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 作为破伤风类毒素，在当前大流行之前和发病后收集的样本中。确定SARS是否- CoV-2感染会改变对其他病原体或疫苗的免疫力。所有研究都将使用样本进行 来自不同寿命的队列，以及那些有癌症诊断和没有癌症诊断的人。在完成时 在建议期内，上述目标将导致我们对T细胞和 项目1中对SARS-CoV-2的B细胞记忆及其与血清学评估的关系。这些进展包括 对我们理解SARS-CoV-2的血清学反应以及最终理解至关重要 对病毒感染甚至疫苗接种的保护性免疫。

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.