Early life B cell responses and inflammation following SARS-CoV-2 infection

SARS-CoV-2 感染后的早期生命 B 细胞反应和炎症

基本信息

批准号：
10696143
负责人：
Genevieve Giny Fouda Amou ou
金额：
$ 70.65万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-17 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10696143
关键词：
18 year old 2019-nCoV Activities of Daily Living Acute Acute Disease Adult Age Antibodies Antibody Response Antigens Avidity B cell repertoire B-Lymphocytes Binding Cessation of life Characteristics Child Child Care Childhood Communities Data Set Development Disease Disease Outcome Enrollment Epitopes Evaluation Fc Receptor Frequencies Genes Genomics Goals HIV HIV Infections Herd Immunity Hospitalization Hospitalized Child Immune Immune response Immunity Immunogenetics Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin Somatic Hypermutation Immunoglobulin Switch Recombination Individual Infection Inflammation Inflammatory Kinetics Knowledge Life Longitudinal Studies Measures Memory B-Lymphocyte Messenger RNA Modernization Monoclonal Antibodies Multisystem Inflammatory Syndrome in Children Natural Immunity Nature Outcome Persons Phenotype Population Predisposition Prevention Proteins Resistance SARS-CoV-2 antibody SARS-CoV-2 infection SARS-CoV-2 variant Sampling Schools Serology Sorting Specificity Syndrome System Testing Time Vaccinated Vaccination Vaccines Variant Viral Virus Work age related antibody-dependent cell cytotoxicity antibody-dependent cellular phagocytosis biophysical properties design glycosylation insight neutralizing antibody novel pandemic disease pathogen post SARS-CoV-2 infection predictive modeling prevent protective effect respiratory virus response school reopening severe COVID-19 vaccination strategy vaccine distribution

项目摘要

Abstract As of March 2021, SARS-CoV-2 has caused more than 50 million infections and 2 million deaths, constituting an unprecedented pandemic in the modern world. While infected individuals rapidly develop IgG responses against the viral Spike after infection, some studies have indicated that individuals with mild infection generate weaker neutralizing Ab responses compared to those with severe disease. The durability of the immune response following natural infection and its afforded protection against subsequent infections and emerging related variants remain unclear. Interestingly, unlike other respiratory viruses, children are rarely develop severe disease following SARS CoV-2 infection. Antibody responses in hospitalized children and those who developed the multisystem inflammatory syndrome (MIS-C) have been characterized, but, there is a gap in knowledge of the magnitude, quality, durability, and breadth of antibody responses in asymptomatic or mildly symptomatic children, responses that may contribute to making children less susceptible to severe infection compared to adults. Moreover, the possibiltiy of reinfection or infection with a novel variant in previously-infected children is not known, making the possibility of restarting congregate settings for children without a childhood vaccine quite challenging. Our overarching goal is to characterize the kinetics, function, breadth, and durability of humoral immune responses elicited by SARS-CoV-2 infection across the pediatric age spectrum in comparison to that of adults. We hypothesize that pediatric immune responses to SARS-CoV-2 infection is distinct from that of adults, and associates with protection against symptomatic disease and durability of immunity. Using samples from two unique ongoing community studies of SARS-CoV-2 infections in adults and children, we will test our hypothesis through the following aims: 1) Define the similarities and differences in the kinetics, magnitude, specificity, function and durability of SARS-CoV-2-specific Ab responses in children and adults; 2) Investigate the breadth and potency of antibody responses in SARS- CoV-2-infected children against established and predicted variants of SARS-CoV-2; and 3) Define the SARS-CoV-2-specific B cell repertoire and characterize the potency of pediatric SARS CoV-2-specific monoclonal antibodies. These evaluations will identify immune correlates of protection against severe disease and provide insights for immunization strategies towards the long term control of SARS CoV-2 which will likely become an endemic pathogen.

抽象的截至 2021 年 3 月，SARS-CoV-2 已造成超过 5000 万人感染，200 万人死亡。死亡，构成现代世界前所未有的大流行。虽然感染者感染后迅速产生针对病毒刺突的 IgG 反应，一些研究表明表明轻度感染的个体产生较弱的中和抗体反应与患有严重疾病的人相比。自然免疫反应的持久性感染及其提供的针对后续感染和新出现的相关变体的保护仍不清楚。有趣的是，与其他呼吸道病毒不同，儿童很少会出现严重的症状 SARS CoV-2 感染后的疾病。住院儿童和那些患有多系统炎症综合征 (MIS-C) 的人已被定性，但是，对抗体的数量、质量、耐久性和广度的认识存在差距无症状或轻度症状儿童的反应，可能有助于与成人相比，儿童不易受到严重感染。此外，先前感染的儿童不存在再次感染或感染新变种的可能性众所周知，为没有童年的儿童重新启动集体环境提供了可能性疫苗相当具有挑战性。我们的首要目标是表征动力学、功能、 SARS-CoV-2 感染引起的体液免疫反应的广度和持久性儿童年龄谱与成人年龄谱的比较。我们假设儿科对 SARS-CoV-2 感染的免疫反应与成人不同，并且与预防症状性疾病和持久免疫力。使用两个样本正在进行的关于成人和儿童 SARS-CoV-2 感染的独特社区研究，我们将测试我们的假设通过以下目标： 1）定义 SARS-CoV-2 特异性抗体反应的动力学、强度、特异性、功能和持久性儿童和成人； 2) 研究 SARS 中抗体反应的广度和效力感染 CoV-2 的儿童针对已确定和预测的 SARS-CoV-2 变种；和 3) 定义 SARS-CoV-2 特异性 B 细胞库并表征儿科药物的效力 SARS CoV-2 特异性单克隆抗体。这些评估将确定免疫相关因素预防严重疾病并为免疫策略提供见解 SARS CoV-2 的长期控制可能会成为一种地方性病原体。