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

项目摘要 COVID-19疫情目前正困扰全球。除了对健康的影响， 人类活动的减少导致了前所未有的经济损失，特别是在 发展中国家的卫生保健和卫生设施不足，甚至在大流行之前。知之甚少 关于人类对SARS-CoV-2的免疫反应的持久性。更好地理解进化 以及在感染后恢复或接种疫苗的个体中抗SARS-CoV-2免疫的持久性 因为它们将指导未来的疫苗工作。 Nussenzweig/Caskey实验室研究了一个队列的初始体液和细胞免疫反应， COVID-19恢复期的个人。通过一系列测定来表征这些样品，所述测定测量： 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.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，我们克隆并鉴定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，初始体液 对SARS-CoV-2的反应是高度可变的，但几乎所有的个体都会发展出某种程度的中和作用， 活动6.2个月后，血清中的中和活性降低了5倍。相反，记忆B 细胞反应继续发展并保持基本不变。有趣的是，有一个收敛的抗体 对SARS-CoV-2的反应可以通过结构分析来解释。除了自然感染， 招募了接受Moderna和辉瑞疫苗的志愿者。B淋巴细胞和 它们产生的抗体将被纵向分析。 有待检验的假设是，对SARS-CoV-2感染或mRNA疫苗接种的体液免疫将 平行减少，但B细胞记忆反应将发散。本提案的总体目标是 确定抗SARS-CoV-2细胞和体液免疫应答的寿命和性质， 检查同一组从COVID-19中康复或接受mRNA疫苗的个体。 这些结果将为我们了解抗SARS-CoV-2免疫的进化和持久性提供信息。 恢复和接种疫苗的个人，并将告知正在进行和未来的疫苗工作。

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.