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University of Rochester Intellectual and Developmental Disabilities Research Center

罗切斯特大学智力与发育障碍研究中心

基本信息

批准号：
10625552
负责人：
JOHN J FOXE
金额：
$ 21.34万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-23 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10625552
关键词：
2019-nCoV Acute Administrative Supplement Adoption Adult Antibodies Antibody-mediated protection Award B-Lymphocytes Binding Biological Assay Blood capillaries Blood specimen COVID-19 COVID-19 vaccine Caring Child Clinical Services Cognitive Communication impairment Communities Complex Computer Models Coronavirus Data Data Set Development Developmental Disabilities Diagnosis Diagnostic Disability phenotype Enrollment Exposure to Gene Deletion Gene Mutation Gene Targeting Genes Genetic Polymorphism Genomics Genotype Goals High Prevalence Human Immune Immune Response Genes Immune Targeting Immune response Immunity Immunoglobulin G Immunologic Memory Impaired cognition Impairment Infection Infection prevention Intellectual and Developmental Disabilities Research Centers Intellectual functioning disability Intellectual scale Intervention Language Link Longitudinal Studies Masks Measurement Measures Mediating Medical Medical History Memory B-Lymphocyte Modeling Nucleoproteins Nutritional Outcome Parents Participant Patient Self-Report Phenotype Prevention strategy Preventive measure Protocols documentation RADx RADx Underserved Populations RNA vaccine Research Respiratory physiology Risk Role SARS-CoV-2 antibody SARS-CoV-2 exposure SARS-CoV-2 immunity SARS-CoV-2 infection SARS-CoV-2 variant Safety Sampling Schools Serum Services Severities Speech Students Subgroup Symptoms Targeted Resequencing Testing Time Time Series Analysis Universities Vaccinated Vaccination Vaccinee Vaccines Variant Vulnerable Populations Work base behavioral phenotyping cross reactivity cytokine disability impact high risk human coronavirus immune function longitudinal analysis nasal swab policy recommendation promoter prospective psychologic recruit response severe COVID-19 vaccine response variants of concern

项目摘要

ABSTRACT School-children with intellectual and developmental disabilities (IDD) are at acute risk for severe COVID-19. Many have compromised immunological and respiratory function, cognitive impairment and complex medical issues. Children with IDD desperately need to attend specialized schools, but this also places them at ultra-high risk of COVID-19 exposure and infection, despite masking, distancing, and vaccination of staff. Critically, we lack longitudinal data on development and persistence of antibody-mediated immunity to COVID-19 for children and staff in IDD-specialized schools, including cross-strain protection, to guide development of vaccination and policy recommendations. This supplement brings together the strengths of the University of Rochester Intellectual and Developmental Disabilities Center and the UR RADx-UP. Under this Administrative Supplement, we propose continuation of our prospective, longitudinal tracking of anti-SARS-CoV-2 antibodies in over 56 IDD students and 282 staff at a specialized school for IDD children. Via RADx-UP, we currently have 7 monthly capillary blood samples per subject analyzed for anti-spike (S) and anti-nucleoprotein (N) IgG against SARS-CoV-2 and variants, and common coronavirus strains (HCoVs: OC43, HKU1, NL63, 229E) measured by the mPLEX-CoV research assay. We will extend this prospective, longitudinal study with an additional 12 months of sampling to capture increases and decreases in SARS-CoV-2 antibody levels. In Aim 1 we will use multidimensional measurement of anti-SARS-CoV-2 and other coronavirus antibodies over 1 year to estimate the rate at which antibodies decrease after vaccination and infection. We will use memory B cell studies to estimate long-lived immune memory and multidimensional analysis of IgG immune repertoire against SARS- CoV-2 variants. In Aim 2, we will link these data, with a comprehensive immune response genotypic and IDD phenotypic analysis. Targeted resequencing of vaccine response genes will provide critical information on immune response associated gene mutations (e.g. cytokine promoter polymorphisms) in neurotypical staff and IDD children, and their influence on anti-SARS-CoV-2 antibody levels. Successful completion of this project will identify decay rates of anti-SARS-CoV-2 IgG in vaccinated subjects, and provide new data on association of IDD phenotyping and immune gene SNPs with vaccine responses.

摘要患有智力和发育障碍（IDD）的学龄儿童面临严重COVID-19的急性风险。许多人的免疫和呼吸功能受损，认知障碍和复杂的医疗问题.患有缺碘症的儿童迫切需要上专门学校，但这也使他们处于极高的贫困水平。尽管工作人员进行了掩蔽、距离和疫苗接种，但仍存在COVID-19暴露和感染的风险。关键是，我们缺乏关于儿童对COVID-19抗体介导的免疫力的发展和持续性的纵向数据和工作人员，包括交叉毒株保护，指导疫苗接种的发展，政策建议。本增刊汇集了罗切斯特大学的优势智力和发育障碍中心和UR RADx-UP。根据本行政补充，我们建议继续我们的前瞻性，纵向跟踪抗SARS-CoV-2抗体在一所缺碘症儿童专门学校的56名缺碘症学生和282名工作人员中，通过RADx-UP，我们目前拥有分析每例受试者每月7次毛细血管血液样本的抗加标（S）和抗核蛋白（N）IgG， SARS-CoV-2及其变异株和普通冠状病毒株（HCoV：OC 43、HKU 1、NL 63、229 E）通过mPLEX-CoV研究测定。我们将扩展这项前瞻性纵向研究，增加12名采样时间长达数月，以捕捉SARS-CoV-2抗体水平的上升和下降。在目标1中，我们将使用多维度测量抗SARS-CoV-2和其他冠状病毒抗体超过1年，以估计接种疫苗和感染后抗体下降的速度。我们将使用记忆B细胞研究，评估针对SARS的长期免疫记忆和IgG免疫库的多维分析- CoV-2变种。在目标2中，我们将把这些数据与全面的免疫反应基因型和IDD联系起来，表型分析疫苗反应基因的靶向重测序将提供以下关键信息：神经型工作人员中免疫应答相关基因突变（例如细胞因子启动子多态性），碘缺乏病儿童血清抗SARS-CoV-2抗体水平及其影响顺利完成该项目将确定接种疫苗受试者中抗SARS-CoV-2 IgG的衰减率，并提供有关 IDD表型和免疫基因SNPs与疫苗应答的关系。