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

• 批准号: 10327992
• 负责人: Michel C Nussenzweig
• 金额: $ 145.45万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 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/10327992
• 关键词: 2019-nCoV; Address; Affinity; 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; base; cohort; cytokine; insight; longitudinal analysis; neutralizing antibody; novel; pandemic coronavirus; pandemic disease; receptor binding; recruit; response; vaccine efficacy; volunteer

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.

项目摘要 Covid-19-19个大流行目前正在吸引世界。除了健康后果，必要的 人类活动的减少导致经济损失没有现代先例，尤其是 发展中国家，即使在大流行之前，医疗保健和卫生也不足够。鲜为人知 关于人类免疫反应对SARS-COV-2的耐用性。更好地理解进化 抗SARS-COV-2免疫的持续性在感染或接种疫苗的个体中 非常需要，因为他们将指导未来的疫苗工作。 Nussenzweig/Caskey实验室研究了队列的初始体液和细胞免疫反应 covid-19-康复个体。这些样品的特征是一系列测量： 1。与SARS-COV-2尖峰蛋白和受体结合结构域的结合抗体的血清水平 （RBD）和2。针对HIV-1和VSV SARS-COV-2伪型病毒和真实性的中和活性 SARS-CoV-2。此外，我们克隆并表征了这些个体产生的抗体， 对RBD上的中和表位有了了解。结果表明最初的体液 对SARS-COV-2的响应高度可变，但几乎所有人都会发展到某种程度的中和 活动。 6.2个月后，血清中和血清中的中和活性减少了5倍。与对比记忆b 细胞反应继续发展并在很大程度上保持完整。有趣的是，抗体会收敛 对SARS-COV-2的响应可以通过结构分析来解释。除了自然感染， 招募了接收现代和辉瑞疫苗的志愿者。 B淋巴细胞和 它们产生的抗体将进行纵向分析。 要测试的假设是对SARS-COV-2感染或mRNA疫苗接种的体液免疫 并行减小，但是B细胞存储器响应会差异。该提议的总体目标是 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-19-19，或接受mRNA疫苗的同一人群。 结果将使我们对抗SARS-COV-2免疫的演变和持久性的理解有关 恢复和接种疫苗的人将为正在进行的和未来的疫苗工作提供信息。