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已引起超过5000万个感染和200万个感染死亡，构成现代世界中空前的大流行。而感染了个人感染后，对病毒尖峰的IgG反应迅速，一些研究具有表明患有轻度感染的人会产生较弱的中和AB反应与患有严重疾病的人相比。自然后免疫反应的耐用性感染及其为随后的感染和新兴变体提供了保护保持不清楚。有趣的是，与其他呼吸道病毒不同，儿童很少出现严重 SARS COV-2感染后的疾病。住院儿童的抗体反应人们已经表征了开发多系统炎症综合征（MIS-C）的人，但是，了解抗体的大小，质量，耐用性和广度的知识差距无症状或轻度症状儿童的反应，可能有助于与成年人相比，使儿童不易受到严重感染的影响。而且，可能在先前感染的儿童中重新感染或感染新型变体的可能不是已知，有可能重新启动没有童年的儿童的聚集环境疫苗很具挑战性。我们的总体目标是表征动力学，功能， SARS-COV-2感染引起的宽度和耐用性免疫反应的耐受性与成年人相比，小儿年龄谱。我们假设该小儿对SARS-COV-2感染的免疫反应与成年人不同，并且与防止有症状的疾病和免疫力耐用性。使用来自两个的样品对成人和儿童中SARS-COV-2感染的独特社区研究，我们将测试我们通过以下目的的假设：1）定义 SARS-COV-2特异性AB反应的动力学，大小，特异性，功能和耐用性儿童和成人； 2）研究SARS- COV-2感染的儿童对SARS-COV-2的既定和预测变体； 3）定义SARS-COV-2特异性B细胞库，并表征儿科的效力 SARS COV-2特异性单克隆抗体。这些评估将确定免疫相关性保护严重疾病，并提供有关免疫策略的见解 SARS COV-2的长期控制可能会成为流行病原体。