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疾病最近已成为具有显著全球发病率和死亡率的主要流行病。 有关SARS-CoV-2免疫反应持久性的几个关键问题仍未得到解答，例如 在轻度至更严重的疾病后，保护性体液免疫和适应性免疫持续多久， 免疫反应是否可以导致长期保护，防止再次感染。结果是 迫切需要建立长期的纵向队列，包括广泛的SARS-CoV-2感染 严重程度和适当匹配的未感染对照来研究这些问题。因此，我们启动了 新型冠状病毒感染的长期影响（LIINC）研究利用我们在UCSF的专业知识， 艾滋病毒和其他感染的纵向队列设计和实施，以识别和收集大样本 从早期恢复期开始，在频繁的时间间隔内检测外周血和唾液。 基于我们在队列实施、病毒学和免疫学方面的强大协作专长，我们将 招募并描述具有一系列初始SARS-CoV-2疾病严重程度（无症状至重度）的成人 和匹配的未感染的对照组我们有两个短期、高影响力的目标，我们希望解决 一旦资金到位，首先，我们将获得、处理和快速分配大量的PBMC 以及大量的血浆、血清和唾液，用于合作研究，以提高SARS-CoV-2的诊断水平 和治疗。我们希望迅速实现这一目标，因为我们有一个现有的议定书，同意程序， 数据库和所有必需的SOP。我们还建立了一个转介网络， 鉴于社区的强烈兴趣，预计将迅速招募这一群体。凭借我们近20年的历史，我们 设计了一个协议和知情同意程序，使我们能够迅速支持学术团体， 基金会、生物技术和制药公司开发诊断和治疗方法。第二、 利用当地调查人员组成的广泛团队，我们将描述建立和衰减适应性， 对SARS-CoV-2的体液免疫应答。更具体地说，我们的目标是扩大LIINC队列， 从早期疾病恢复期频繁收集大量血浆、血清和唾液（21 从最初症状出现后30天到恢复后24个月，确定SARS-CoV-2感染对 病毒特异性CD 4和CD 8 T细胞应答，直至症状发作后24个月，并定义 感染后抗体应答的长期动力学和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。 并提供关于免疫疗法和疫苗开发的关键信息。