Scientific Project 3: Covid Immune response to SARS-CoV-2 natural infection followed by vaccination

HIPC3科学项目3：对SARS-CoV-2自然感染的免疫反应，然后接种疫苗 摘要 该项目将表征SARS-CoV-2自然感染的先天和获得性免疫反应。 设置轻度疾病和后续疫苗接种。我们将定义与病毒减少相关的特征 脱落，进展为PASC或长COVID，以及获得性免疫反应的幅度 恢复期和接种疫苗后。我们的方法使用尖端的多组单细胞技术来 剖析先天免疫反应和获得性免疫反应，并确定保护、疫苗反应和 PASC。我们将1.定义急性感染期间的先天免疫反应，并检验假设 病毒排出持续时间的个体间差异部分是由先天反应的差异调节的。这些 分析还将包括不同的参与者，以确定按种族/族裔划分的潜在贡献。2.追踪 T细胞对自然感染和后续疫苗免疫应答的演变和动力学。我们假设 特定的靶向表位和表型在短暂的病毒脱落中将更具保护性，而疫苗 诱导独特的、具有保护性的T细胞，这是恢复期的剧目中没有的。这些研究还将 确定关键的辅助性T细胞表型以增强对自然感染的体液和细胞反应 还有疫苗。这些特征也将与先天免疫特征相关联，以识别先天适应性 协调事件3.描述PASC感染和康复过程中的免疫反应。 我们将分析从急性感染到恢复期的先天免疫和获得性免疫，以了解 与成功恢复相比，PASC的炎症和抗病毒反应轨迹可能不同。这些 将使关于PASC的致病机制和治疗靶点的假说成为可能 机械装置。这些结果将改善临床结果，改善现有PASC患者的治疗，以及 可以指导疫苗的开发和助推剂。总体而言，我们的纵向分析将免疫 在整个疾病过程中，对具体功能结果的反应，包括病毒脱落持续时间、PASC和 疫苗反应。

HIPC3 Scientific Project 3: Immune response to SARS-CoV-2 natural infection followed by vaccination Abstract This project will characterize the innate and adaptive immune response to SARS-CoV-2 natural infection in the setting of mild disease and follow-on vaccination. We will define signatures correlating with reduced viral shedding, progression to PASC or long COVID, and magnitude of adaptive immune responses in convalescence and after vaccination. Our approach uses cutting-edge multi-omic single-cell technologies to dissect the innate and adaptive immune response and identify correlates of protection, vaccine response, and PASC. We will 1. Define the innate immune response during acute infection and test the hypothesis that interindividual variation in viral shedding duration is partly regulated by differences in innate response. These analyses will also include diverse participants to identify potential contributions by race/ethnicity. 2. Track the evolution and kinetics of T cell responses to natural infection and follow-on vaccination. We hypothesize that specific targeted epitopes and phenotypes will be more protective in short viral shedding, and that vaccines induce unique, protective T cells that are not found in the convalescent repertoire. These studies will also identify key helper T cell phenotypes for mounting robust humoral and cellular responses to natural infection and vaccine. These signatures will also be correlated with innate immune signatures to identify innate-adaptive coordination events 3. Characterize the immune response throughout infection and convalescence in PASC. Innate and adaptive immunity will be analyzed from acute infection through convalescence to understand how inflammation and antiviral response trajectories may differ in PASC compared to successful recovery. These will enable hypotheses on the causal mechanisms of PASC and therapeutic targets from ongoing pathogenic mechanisms. These results will enable improved clinical outcomes, treatment of existing PASC patients, and can guide vaccine developments and boosters. Overall, our longitudinal analysis will associate immune responses throughout disease to concrete functional outcomes including duration of viral shedding, PASC, and vaccine response.