Molecular Biology of RV-C and its Asthma-related Receptor, CDHR3

RV-C 及其哮喘相关受体 CDHR3 的分子生物学

• 批准号: 10327681
• 负责人: ANN C. PALMENBERG
• 金额: $ 40.35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-21 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10327681
• 关键词: 2019-nCoV; Allergic; Antibodies; Antibody Diversity; Antibody Response; Asthma; B cell repertoire; Binding; Biological Assay; Birth; Blood specimen; COVID-19; COVID-19 surveillance; Child; Childhood; Cohort Studies; Common Epitope; Coronavirus; Country; Data; Development; Disease Outbreaks; Enrollment; Epitopes; Family; Farming environment; Future; Human; Hypersensitivity; Immune; Immune system; Individual; Infant; Infection; Laboratories; Life; Lung diseases; Machine Learning; Microbe; Molecular Biology; Monitor; Morbidity - disease rate; Nose; Pattern; Peripheral Blood Mononuclear Cell; Population; Predisposition; Prevention; Proteome; Rhinovirus; SARS-CoV-2 infection; Serology; Serum; Severities; Severity of illness; Societies; Specimen; Symptoms; Testing; Vaccine Design; Viral; Viral Antibodies; Viral Structural Proteins; Virus; Wisconsin; burden of illness; cohort; cost; cross reactivity; immunogenic; infection risk; new technology; novel coronavirus; parent grant; public health emergency; receptor; respiratory; respiratory virus; response; study population; surveillance study

The new coronavirus outbreak that begin in December 2019 has created a global public health emergency. This has led to an intense search to identify factors that contribute to the susceptibility and severity of illness. We recently developed an array to identify antibody-binding epitopes for rhinoviruses. Data from these arrays can be combined with information about viral protein structure to identify highly immunogenic regions for respiratory viruses. We propose to expand this array to include linear epitopes that represent the entire proteome of SARS-CoV-2 and all other common coronaviruses that infect humans (OC43, NL63, etc.). The study population will include children from the COAST, WISC and URECA birth cohort studies who are also participating in the HEROS SARS-CoV-2 surveillance study. As part of routine cohort activities, these children undergo serial sampling of blood and nasal secretions that we can analyze using the array to determine individual patterns of antiviral antibody epitope recognition. We hypothesize that the pattern and quantity of antibody specific for epitopes of common coronaviruses contributes to the susceptibility to SARS-CoV-2 infection and illness. We propose three specific aims that will utilize sera obtained from children before and after HEROS-confirmed infection with SARS-CoV-2. First, in specimens obtained pre-infection we will use the array to identify patterns of antibody epitope recognition to common childhood coronaviruses, assess cross-reactivity with SARS-CoV-2, and determine whether cross-reactivity is associated with protection against infection or illness. In the second aim, we will determine whether the diversity of antibody responses to common respiratory viruses is associated with a reduced risk of infection or illness. Finally, in the third aim we will describe antibody binding patterns before and after known COVID-19 cases to identify candidate regions that are immunogenic and neutralizing. To accomplish this aim, we will perform micro-neutralization assays (available in the BSL3 laboratory of Dr. Kristen Bernard, UW Madison) on convalescent sera or nasal secretions from children who developed symptomatic infection. This information will be analyzed together with pre- and post-infection array data using machine learning approaches to identify neutralizing epitopes. Identifying patterns of serologic responses that are crossprotective could help to identify susceptible individuals in the population and direct the design of vaccines to current and future viruses.

2019年12月开始的新型冠状病毒爆发造成了全球公共卫生紧急情况。这 导致了一个紧张的搜索，以确定因素，有助于易感性和疾病的严重性。我们 最近开发了一种阵列来鉴定鼻病毒的抗体结合表位。来自这些阵列的数据可以 结合有关病毒蛋白质结构的信息，以鉴定呼吸道感染的高免疫原性区域。 病毒我们建议扩展该阵列，以包括代表SARS-CoV-2和所有其他感染人类的常见冠状病毒（OC 43，NL 63等）的整个蛋白质组的线性表位。研究人群将 包括来自COAST、WISC和URECA出生队列研究的儿童，他们也参加了 HEROS SARS-CoV-2监测研究。作为常规队列活动的一部分，这些儿童接受系列 血液和鼻腔分泌物的采样，我们可以使用阵列进行分析，以确定 抗病毒抗体表位识别。我们假设，特异性抗体的模式和数量， 常见冠状病毒的表位有助于对SARS-CoV-2感染和疾病的易感性。我们 提出了三个具体目标，将利用从HEROS确认前后的儿童中获得的血清 感染了SARS-CoV-2首先，在感染前获得的标本中，我们将使用阵列来识别模式 识别常见儿童冠状病毒的抗体表位，评估与SARS-CoV-2的交叉反应性， 并确定交叉反应性是否与预防感染或疾病有关。在第二 目的：我们将确定对常见呼吸道病毒的抗体应答的多样性是否与 降低感染或患病的风险。最后，在第三个目标中，我们将描述抗体结合模式， 以及在已知的COVID-19病例之后，以鉴定具有免疫原性和中和性的候选区域。到 为了实现这一目标，我们将进行微量中和试验（可在Kristen博士的BSL 3实验室获得 Bernard，UW麦迪逊）对出现症状的儿童的恢复期血清或鼻分泌物进行了研究。 感染这些信息将与感染前和感染后的阵列数据一起使用机器进行分析 学习鉴定中和表位的方法。识别交叉保护的血清学应答模式有助于识别人群中的易感个体，并指导疫苗的设计， 当前和未来的病毒