Longitudinal Immunological Impact of SARS-CoV-2 Infection

SARS-CoV-2 感染的纵向免疫学影响

• 批准号: 10265644
• 负责人: Timothy Jensen Henrich
• 金额: $ 73.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265644
• 关键词: 2019-nCoV; Academic support; Address; Adult; Antibody Response; Biotechnology; Blood Cells; Blood Plasma Volume; CD8-Positive T-Lymphocytes; COVID-19 diagnosis; COVID-19 severity; Clinical; Communities; Consent; Convalescence; Databases; Development; Diagnostic; Disease; Enrollment; Foundations; Funding; Goals; HIV; Humoral Immunities; Immune response; Immunity; Immunologics; Immunology; Immunotherapy; Individual; Infection; Informed Consent; Kinetics; Lead; Longitudinal cohort; Maintenance; Medical; Mononuclear; Morbidity - disease rate; Participant; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Plasma; Process; Protocols documentation; Recording of previous events; Recovery; Research; Research Personnel; SARS-CoV-2 infection; Saliva; Secure; Severities; Symptoms; T cell response; T-Lymphocyte; Viral; adaptive immunity; cohort; comorbidity; demographics; design; improved; interest; mortality; novel coronavirus; pandemic disease; peripheral blood; recruit; response; vaccine development; virology

SARS-CoV-2 disease has recently become a major pandemic with significant global morbidity and mortality. Several key questions regarding the durability of immune responses to SARS-CoV-2 remain unanswered, such as how long protective humoral and adaptive immunity persist following mild to more severe disease, and whether or not the immune response may lead to longer-term protection from re-infection. As a result, there is urgent need to develop long-term, longitudinal cohorts that include a wide spectrum of SARS-CoV-2 infection severity and appropriately matched uninfected controls to study such questions. As a result, we initiated the Long-term Impact of Infection with Novel Coronavirus (LIINC) study leveraging our expertise at UCSF with longitudinal cohort design and implementation for HIV and other infections, to identify and collect largevolumes of peripheral blood and saliva during frequent intervals starting during the early convalescent period. Building on our strong collaborative expertise in cohort implementation, virology and immunology, we will recruit and characterize adults with a range of initial SARS-CoV-2 disease severity (asymptomatic to severe) and matched, uninfected controls. We have two short-term, high-impact objectives that we expect to address rapidly, once funding is secured. First, we will obtain, process, and rapidly distribute large numbers of PBMCs and large volumes of plasma, serum and saliva for collaborative research to improve SARS-CoV-2 diagnosis and treatment. We expect to achieve this objective rapidly as we have an existing protocol, consent process, database and all of the required SOPs. We also have an established referral network already in place and expect to rapidly enroll the cohort given intense community interest. Leveraging our nearly 20 year history, we have designed a protocol and informed consent process that will allow us to rapidly support academic groups, foundations, and biotechnology and pharmaceutical companies to develop diagnostics and therapies. Second, using an extensive team of local investigators, we will characterize the establishment and decay adaptive and humoral immune response to SARS-CoV-2. More specifically, our aims are to expand the LIINC cohort to collect large volumes of plasma, serum and saliva at frequent intervals from early disease convalescence (21 days following initial symptoms) to 24 months after recovery, determine the impact of SARS-CoV-2 infection on viral-specific CD4 and CD8 T cell responses up to 24 months following onset of symptoms, and define the long-term kinetics of the antibody response and the duration of protective immunity following infection with SARS-CoV-2. Together, results from our studies would have implications on duration of protective immunity and provide key information on immunotherapy and vaccine development.

SARS-COV-2疾病最近已成为一个主要的大流行，具有明显的全球发病率和死亡率。 关于SARS-COV-2免疫反应的耐用性的几个关键问题仍未得到答复，例如 由于在轻度至更严重的疾病之后，保护性的体液和适应性免疫持续了多长时间，并且 免疫反应是否可能导致长期保护免于再感染。结果，有 迫切需要开发长期的纵向人群，包括广泛的SARS-COV-2感染 严重性并适当匹配未感染的对照，以研究此类问题。结果，我们启动了 通过新型冠状病毒（LIINC）研究的长期影响，利用我们在UCSF的专业知识 为艾滋病毒和其他感染的纵向队列设计和实施，以识别和收集大量 从恢复期初期开始，在频繁的间隔内频繁间隔。 在我们在队列实施，病毒学和免疫学方面的强大协作专业知识的基础上，我们将 招募和表征成年人，具有一系列初始SARS-COV-2疾病严重程度（无症状至重度） 并匹配未感染的控件。我们有两个短期的高影响目标，我们期望解决 一旦获得资金，迅速。首先，我们将获得，处理和快速分发大量的PBMC 以及大量的血浆，血清和唾液进行协作研究，以改善SARS-COV-2诊断 和治疗。我们希望随着我们拥有现有协议，同意过程， 数据库和所有必需的SOP。我们还已经建立了一个已建立的推荐网络，并且 鉴于社区的强烈兴趣，期望迅速招募队列。利用我们将近20年的历史，我们 已经设计了一个协议和知情同意程序，这将使我们能够迅速支持学术团体， 基金会以及生物技术和制药公司开发诊断和疗法。第二， 我们将使用大量的当地调查人员团队来表征机构和衰败的自适应和 对SARS-COV-2的体液免疫反应。更具体地说，我们的目的是将Liinc队列扩展到 从早期疾病康复中频繁间隔收集大量血浆，血清和唾液（21 恢复后至24个月后，最初症状后的几天，确定SARS-COV-2感染对 症状发作后长达24个月的病毒特异性CD4和CD8 T细胞反应，并定义 抗体反应的长期动力学以及感染后保护性免疫的持续时间 SARS-CoV-2。总之，我们的研究结果将对保护性免疫的持续时间产生影响 并提供有关免疫疗法和疫苗开发的关键信息。