The longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responses

抗 SARS-CoV-2 细胞和体液免疫反应的寿命和性质

基本信息

批准号：
10841240
负责人：
Michel C Nussenzweig
金额：
$ 98.31万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-03 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10841240
关键词：
2019-nCoV Address Affinity Animal Experiments Animals Antibodies Antibody Response Antigens B-Lymphocytes Binding Biological Assay CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes COVID-19 COVID-19 pandemic Cell-Mediated Cytolysis Cells Cellular Immunity Clinical Collaborations Coronavirus Economics Enzyme-Linked Immunosorbent Assay Epitopes Evolution FDA Emergency Use Authorization Flow Cytometry Future Goals HIV-1 Health Healthcare Human Human Activities Humoral Immunities Immune response Immunization Immunoglobulin A Immunoglobulin G Immunoglobulin M Individual Infection Laboratories Laboratory Study Longevity Macaca Measures Mediating Memory B-Lymphocyte Messenger RNA Modernization Monoclonal Antibodies Mus Nature Peptides Plasma Property Protein Binding Domain RNA vaccination RNA vaccine Rice SARS-CoV-2 antibody SARS-CoV-2 immunity SARS-CoV-2 infection SARS-CoV-2 spike protein Sampling Sanitation Scheme Series Serology Serum Symptoms T cell response Testing Time Vaccinated Vaccination Vaccinee Vaccines Variant Vesicular stomatitis Indiana virus Viral Virus World Health cohort cytokine grasp insight longitudinal analysis neutralizing antibody novel pandemic coronavirus pandemic disease receptor binding recruit response vaccine efficacy volunteer

项目摘要

Project Summary The COVID-19 pandemic is currently gripping the world. Aside from the health consequences, the necessary decrease in human activity has resulted in economic losses without modern precedent, especially in the developing world where health care and sanitation were not sufficient even prior to the pandemic. Little is known about the durability of the human immune responses to SARS-CoV-2. A better understanding of the evolution and persistence of anti SARS-CoV-2 immunity in individuals who recover for the infection or who are vaccinated are critically needed as they will guide future vaccine efforts. The Nussenzweig/Caskey laboratory studied the initial humoral and cellular immune responses of a cohort of COVID-19 convalescent individuals. These samples were characterized by a series of assays that measure: 1. Serum levels of binding antibodies to the SARS-CoV-2 spike protein (S) and the receptor binding domain (RBD) and 2. Neutralizing activity against HIV-1 and VSV SARS-CoV-2 pseudotyped viruses and authentic SARS-CoV-2. In addition, we cloned and characterized the antibodies produced by these individuals and developed an understanding of the neutralizing epitopes on the RBD. The results showed that the initial humoral responses to SARS-CoV-2 are highly variable but that nearly all individuals develop some level of neutralizing activity. Neutralizing activity in serum decreases after by a factor of 5 after 6.2 months. In contrast memory B cell responses continue to evolve and remain largely intact. Interestingly, there was a convergence of antibody responses to SARS-CoV-2 that could be explained by structural analysis. In addition to natural infection, a cohort of volunteers that received the Moderna and Pfizer vaccines was recruited. The B lymphocytes and the antibodies they produce will be analyzed longitudinally. The hypothesis to be tested is that humoral immunity to SARS-CoV-2 infection or mRNA vaccination will decrease in parallel, but that B cell memory responses will diverge. The overall goal of this proposal is to determine the longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responses by re- examining the same cohort of individuals who either recovered from COVID-19 or received an mRNA vaccine. The results will inform our understanding of the evolution and persistence of anti- SARS-CoV-2 immunity in recovered and vaccinated individuals and will inform ongoing and future vaccine efforts.

项目概要目前，新冠肺炎 (COVID-19) 大流行正在席卷全球。除了健康后果外，必要的人类活动的减少造成了现代史无前例的经济损失，特别是在即使在大流行之前，发展中国家的医疗保健和卫生设施也不足。鲜为人知关于人类对 SARS-CoV-2 免疫反应的持久性。更好地理解进化感染后康复或接种疫苗的个体中抗 SARS-CoV-2 免疫力的持续性迫切需要它们，因为它们将指导未来的疫苗工作。 Nussenzweig/Caskey 实验室研究了一组人的初始体液和细胞免疫反应 COVID-19 康复者。这些样品通过一系列测定来表征： 1. SARS-CoV-2刺突蛋白（S）和受体结合域结合抗体的血清水平 (RBD) 和 2. 针对 HIV-1 和 VSV SARS-CoV-2 假型病毒和真实病毒的中和活性 SARS-CoV-2。此外，我们克隆并表征了这些个体产生的抗体，并加深了对 RBD 上中和表位的了解。结果表明，初始体液对 SARS-CoV-2 的反应差异很大，但几乎所有个体都会产生一定程度的中和反应活动。 6.2 个月后，血清中和活性降低了 5 倍。对比记忆B 细胞反应继续进化并基本保持完整。有趣的是，抗体的聚合对 SARS-CoV-2 的反应可以通过结构分析来解释。除了自然感染之外，队列招募了接受 Moderna 和辉瑞疫苗的志愿者。 B 淋巴细胞和他们产生的抗体将被纵向分析。要测试的假设是，针对 SARS-CoV-2 感染或 mRNA 疫苗接种的体液免疫会平行减少，但 B 细胞记忆反应会发散。该提案的总体目标是通过重新确定抗 SARS-CoV-2 细胞和体液免疫反应的寿命和性质检查从 COVID-19 中康复或接受 mRNA 疫苗的同一组个体。这些结果将帮助我们了解抗 SARS-CoV-2 免疫的进化和持续性康复和接种疫苗的个人，并将为正在进行和未来的疫苗工作提供信息。