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

项目摘要 新冠肺炎大流行目前正席卷全球。除了对健康的影响，必要的 人类活动的减少造成了前所未有的经济损失，特别是在 在发展中国家，卫生保健和卫生设施甚至在大流行之前就不够充分。鲜为人知 关于人类对SARS-CoV-2的免疫反应的持久性。更好地理解进化 在感染康复或接种疫苗的个人中，抗SARS-CoV-2免疫的持久性 是非常需要的，因为它们将指导未来的疫苗努力。 Nussenzweig/Caskey实验室研究了一个队列的初始体液和细胞免疫反应 新冠肺炎的康复者。这些样品通过一系列测试进行了表征，这些测试包括： 1.血清抗SARS-CoV-2刺突蛋白结合抗体水平(S)及其受体结合域 (RBD)和2.对HIV-1和VSV SARS-CoV-2伪型病毒的中和活性和真品 SARS-CoV-2。此外，我们克隆并鉴定了这些个体产生的抗体和 发展了对RBD中和表位的理解。结果表明，最初的体液 对SARS-CoV-2的反应是高度可变的，但几乎所有人都会产生某种程度的中和 活动。6.2个月后，血清中和活性下降5倍。与之形成对比的是存储器B 细胞反应继续进化，并基本保持不变。有趣的是，抗体汇聚在一起。 对SARS-CoV-2的应答可以用结构分析来解释。除了自然感染，还有一个队列 招募了接受莫德纳和辉瑞疫苗的志愿者。B淋巴细胞与 他们产生的抗体将被纵向分析。 需要检验的假设是，对SARS-CoV-2感染的体液免疫或mRNA疫苗接种将 同时减少，但B细胞的记忆反应将会分化。这项提案的总体目标是 测定抗SARS-CoV-2细胞和体液免疫应答的寿命和性质 研究了同一群从新冠肺炎康复或接受信使核糖核酸疫苗接种的人。 这些结果将有助于我们理解抗SARS-CoV-2免疫的演变和持久性。 已康复和接种疫苗的个人，并将为正在进行的和未来的疫苗工作提供信息。

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.