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

科学项目 3：疫苗接种后对 SARS-CoV-2 自然感染的 Covid 免疫反应

• 批准号: 10631112
• 负责人: Gregory Lee Szeto
• 金额: $ 11.72万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-19 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631112
• 关键词: 2019-nCoV; Acute; Affect; Age; Antibodies; Antiviral Response; B-Lymphocytes; Biological Assay; Biological Markers; Biological Response Modifiers; CD8-Positive T-Lymphocytes; COVID-19; Cellular Immunity; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Characteristics; Chronic; Clinical; Convalescence; Cytometry; Data; Diagnostic; Disease; Epitopes; Ethnic Origin; Event; Evolution; Flow Cytometry; Future; Goals; HIV; Helper-Inducer T-Lymphocyte; Human Herpesvirus 4; Humoral Immunities; Immune; Immune response; Immunity; Immunization; Immunologics; Infection; Inflammation; Inflammatory; Innate Immune Response; Kinetics; Long COVID; Longitudinal cohort; Malaria; Maps; Molecular; Natural Immunity; Outcome; Participant; Pathogenicity; Patients; Peptide/MHC Complex; Phenotype; Post-Acute Sequelae of SARS-CoV-2 Infection; Prevalence; Prognostic Marker; Proteomics; RNA vaccine; Race; Recovery; SARS-CoV-2 infection; Serum; Site; Subgroup; Symptoms; Syndrome; Systems Biology; T cell receptor repertoire sequencing; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic Intervention; Time; Vaccination; Vaccine Design; Vaccines; Variant; Viral Load result; Viral Respiratory Tract Infection; Virus; Virus Shedding; Work; acute infection; adaptive immune response; adaptive immunity; burden of illness; cohort; flu; follow-up; functional outcomes; improved; inter-individual variation; longitudinal analysis; multiple omics; new therapeutic target; persistent symptom; predictive marker; racial diversity; response; severe COVID-19; sex; single cell technology; therapeutic target; vaccine development; vaccine efficacy; vaccine response; vaccine-induced immunity

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.

HIPC 3科学项目3：SARS-CoV-2自然感染后接种疫苗的免疫反应 摘要 该项目将描述SARS-CoV-2自然感染的先天性和适应性免疫反应， 轻度疾病的设置和后续疫苗接种。我们将定义与减少病毒相关的特征 脱落，进展为PASC或长期COVID，以及 疫苗接种后和恢复期。我们的方法使用尖端的多组学单细胞技术， 剖析先天性和适应性免疫反应，并确定保护，疫苗反应， PASC。我们将1。定义急性感染期间的先天免疫反应，并检验以下假设： 病毒脱落持续时间的个体间差异部分受先天反应差异的调节。这些 分析还将包括不同的参与者，以确定种族/族裔的潜在贡献。2.跟踪 T细胞对自然感染和后续疫苗接种应答的演变和动力学。我们假设 特异性靶向表位和表型在短期病毒脱落中更具保护性， 诱导独特的保护性T细胞，这些T细胞在恢复期的所有功能中都没有发现。这些研究还将 鉴定关键辅助性T细胞表型，以建立对自然感染的强大体液和细胞应答 和疫苗。这些特征也将与先天免疫特征相关联，以识别先天适应性 协调活动3.描述PASC感染和恢复期的免疫反应。 从急性感染到恢复期的先天免疫和适应性免疫将被分析， PASC的炎症和抗病毒反应轨迹可能与成功恢复不同。这些 将使关于PASC的因果机制和治疗靶点的假设能够从正在进行的致病性 机制等这些结果将改善临床结局，治疗现有PASC患者， 可以指导疫苗开发和加强剂。总的来说，我们的纵向分析将免疫 整个疾病期间对具体功能结局的反应，包括病毒脱落持续时间、PASC，以及 疫苗反应。