Adaptive Immunity and Persistent SARS-CoV-2 Replication

适应性免疫和持续 SARS-CoV-2 复制

• 批准号: 10558542
• 负责人: Suresh B Boppana
• 金额: $ 67.54万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10558542
• 关键词: 11 year old; 2019-nCoV; ACE2; Adult; Adverse effects; Adverse event; Age; Alabama; Antibodies; Antibody Response; Antigens; Appointment; Binding; Biological Assay; Blood specimen; COVID-19; COVID-19 detection; COVID-19 mortality; COVID-19 pandemic; COVID-19 susceptibility; COVID-19 vaccine; Cardiac; Cardiology; Cardiotoxicity; Case Report Form; Cessation of life; Chemotherapy-Oncologic Procedure; Child; Child Health; Childhood; Clinic; Clinical; Clinical Sciences; Data; Disease; Disease Outcome; Dose; Effectiveness; Enrollment; Evaluation; Faculty; Flow Cytometry; Hematological Disease; Hematology; Hospitalization; Immune; Immune response; Immune system; Immunity; Immunization; Immunocompetence; Immunocompromised Host; Immunologics; Impairment; Individual; Infrastructure; Laboratories; Link; Malignant Neoplasms; Masks; Measurement; Measures; Mediating; Messenger RNA; Monitor; Myocarditis; Nature; Organ; Participant; Patient-Focused Outcomes; Patients; Pediatric Oncology; Pediatrics; Pericarditis; Peripheral Blood Mononuclear Cell; Play; Policies; Population; Primary Health Care; RNA; RNA vaccination; RNA vaccine; Recommendation; Reporter; Reporting; Research; Respiratory System; Risk; Role; SARS-CoV-2 B.1.617.2; SARS-CoV-2 antibody; SARS-CoV-2 exposure; SARS-CoV-2 infection; Safety; Sample Size; Secondary to; Serum; Sickle Cell Anemia; Social Distance; Solid; Specimen; Standardization; Symptoms; T cell response; T-Lymphocyte; Teenagers; Time; Translational Research; Troponin; Upper respiratory tract; Vaccinated; Vaccination; Vaccines; Variant; Viral; Viral Antibodies; Virus; Virus Shedding; Visit; Vulnerable Populations; adaptive immunity; age group; base; breakthrough infection; chemotherapy; clinical care; clinical center; cohort; comparison group; coronavirus disease; demographics; follow-up; immunogenicity; immunomodulatory therapies; improved; infection rate; insight; nasal swab; novel; novel coronavirus; pandemic disease; particle; peripheral blood; post SARS-CoV-2 infection; prevent; prospective; respiratory; response; sample collection; seasonal coronavirus; telehealth; vaccine candidate; vaccine development; vaccine efficacy; young adult

Project Summary/Abstract The novel coronavirus SARS-CoV-2 (SARS2) pandemic has so far infected greater than 65 million individuals and resulted in almost 850,000 deaths in the US. Although it has been suggested that adaptive immunity plays an important role in improving clinical outcomes of patients infected with SARS2, correlates of protective immune responses have not been defined. Also, an explanation for the variability in clinical disease and outcome in patients with SARS2 infection has not been explained based on qualitative and quantitative antiviral immune responses. Studies in immunocompromised adults have shown somewhat decreased efficacy of SARS2 mRNA vaccines and increased rates of breakthrough infections. A significant proportion of children with deficits in immune competence secondary to cancer chemotherapy and hematologic disorders were observed to have blunted antiviral antibody responses following SARS2 infection and shed virus for prolonged periods of time (>6 weeks) in the upper respiratory tract. Together, these findings raise the possibility that children with specific qualitative or quantitative deficits in adaptive immunity may generate somewhat blunted or decreased immune responses to SARS2 vaccines. The safety and immunogenicity of SARS2 mRNA vaccine in young children especially those with compromised immune responses have not been examined. The objective of the proposed study is to define quantitative and qualitative antiviral antibody responses and T cell immunity responses generated following SARS2 mRNA vaccination in a cohort of children with varying levels immune responsiveness and compare those with age-match healthy children. Defining relationships between variations in immune competence and vaccine-mediated protection could provide a novel insight into the level and nature of adaptive immunity that can produce robust immune responses to SARS2 mRNA vaccine. Our studies will also determine the safety of SARS2 mRNA vaccine in children with impaired immunity and in a group of healthy children. Analysis of the quality and quantity of SARS2 antibody and T cell responses to the mRNA vaccine will help develop vaccine candidates or adapt existing vaccines to provide effective protection. In addition, the proposed studies will also examine the durability of vaccine-mediated immunity and the need for additional doses that can protect this vulnerable group of children.

项目总结/文摘