Immunologic Signatures of SARS-CoV-2 Vaccination and Disease

摘要 研发SARS-CoV-2疫苗可能是结束新冠肺炎大流行的关键。然而，a 知识方面的关键差距是缺乏对人类SARS-CoV-2免疫相关因素的了解。 我们的初步数据表明，抗体与非人类接种疫苗后的保护相关。 灵长类动物和独特的抗体功能谱似乎可以预测自然感染的疾病结局 人类。我们的数据还表明，抗体图谱正在趋同，包括抗原结合域驱动 中和和Fc介导的效应器功能驱动保护性免疫。知识的另一个缺口是 人类感染SARS-CoV-2和接种疫苗后保护性免疫的持久性未知。 我们的初步数据表明，在人类感染SARS-CoV-2后，抗体效价可能会迅速下降， 但需要更大规模的研究和更长时间的随访来确定恢复期抗体反应的动力学。 个人。此外，疫苗引发的抗体反应的持久性仍有待确定。 我们假设康复期和接种疫苗的人都会产生功能性抗体。 与恒河猴抗SARS-CoV-2挑战的疫苗保护相关的签名。 我们进一步假设，接种疫苗将产生比诱导的抗体更持久的抗体。 通过自然感染，可以定义耐受性的免疫学相关性。 具体目标1.确定感染SARS-CoV-2或接种疫苗后相关的抗体谱 有保护的人。我们将剖析SARS-CoV-2感染者所引发的功能性抗体反应 以及在接种SARS-CoV-2疫苗的个体中提供对保护相关因素的洞察。 特定目的2.确定SARS-CoV-2抗体反应持久性的免疫学相关性 在感染或接种疫苗之后。我们将比较SARS诱导的抗体反应的持久性- CoV-2感染和接种的个体，我们将定义耐受性的免疫学相关性。

ABSTRACT The development of a SARS-CoV-2 vaccine may be critical to ending the COVID-19 pandemic. However, a critical gap in knowledge is the lack of understanding of correlates of SARS-CoV-2 immunity in humans. Our preliminary data suggest that antibodies correlate with protection following vaccination in nonhuman primates and that unique antibody functional profiles appear to predict disease outcome in natural infection in humans. Our data also point to a converging antibody profile, including both the antigen-binding domain driving neutralization and Fc-mediated effector functions driving protective immunity. Another gap in knowledge is the unknown durability of protective immunity following SARS-CoV-2 infection and vaccination in humans. Our preliminary data suggest that antibody titers may wane quickly following SARS-CoV-2 infection in humans, but larger studies and longer follow-up are needed to define the kinetics of antibody responses in convalescent individuals. Moreover, the durability of vaccine-elicited antibody responses remains to be determined. We hypothesize that both convalescent and vaccinated humans will develop the functional antibody signature that correlates with vaccine protection against SARS-CoV-2 challenge in rhesus macaques. We further hypothesize that vaccination will induce antibodies with greater durability than those induced by natural infection and that an immunologic correlate of durability can be defined. Specific Aim 1. Define the antibody profiles following SARS-CoV-2 infection or vaccination that correlate with protection. We will dissect the functional antibody responses elicited in SARS-CoV-2 infected individuals and in SARS-CoV-2 vaccinated individuals to provide insight into correlates of protection. Specific Aim 2. Define the immunologic correlates of durability of SARS-CoV-2 antibody responses following infection or vaccination. We will compare the durability of antibody responses induced in SARS- CoV-2 infected and vaccinated individuals, and we will define an immunologic correlate of durability.