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.

项目摘要/摘要 迄今为止，新型的冠状病毒SARS-COV-2（SARS2）大流行感染了6500万 在美国，个人并导致近85万人死亡。虽然有人建议 自适应免疫在改善感染患者的临床结局中起着重要作用 SARS2，尚未定义保护性免疫反应的相关性。另外，解释了 尚未解释SARS2感染患者的临床疾病和结果的变异性 基于定性和定量抗病毒免疫反应。免疫功能低下的研究 成年人显示SARS2 mRNA疫苗的疗效有所降低，率提高 突破性感染。很大一部分患有免疫能力缺陷的儿童 观察到癌症化学疗法和血液学疾病的继发性抗病毒药 SARS2感染后的抗体反应和病毒长时间（> 6周） 在上呼吸道中。这些发现共同提出了特定的儿童 自适应免疫中的定性或定量缺陷可能会产生一些钝性或减少 对SARS2疫苗的免疫反应。 SARS2 mRNA疫苗的安全性和免疫原性 尚未检查幼儿，尤其是那些免疫反应受损的孩子。这 拟议的研究的目的是定义定量和质量抗病毒药抗体反应以及 SARS2 mRNA接种后产生的T细胞免疫反应在一群儿童中 不同水平的免疫反应能力，并将年龄匹配健康的儿童进行比较。定义 免疫能力的变化与疫苗介导的保护之间的关系可以提供 对自适应免疫的水平和性质的新颖洞察力，可以产生可靠的免疫 对SARS2 mRNA疫苗的反应。我们的研究还将确定SARS2 mRNA的安全性 免疫力受损和一组健康儿童的儿童的疫苗。分析质量和 SARS2抗体的数量和对mRNA疫苗的T细胞反应将有助于开发疫苗 候选或调整现有疫苗以提供有效的保护。另外，提出的研究 还将检查疫苗介导的免疫力的耐用性，以及需要的额外剂量 保护这一脆弱的儿童。