Immunologic Signatures of SARS-CoV-2 Vaccination and Disease

SARS-CoV-2 疫苗接种和疾病的免疫学特征

• 批准号: 10221341
• 负责人: Galit Alter
• 金额: $ 147.8万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221341
• 关键词: 2019-nCoV; Antibodies; Antibody Response; Antibody titer measurement; Automobile Driving; COVID-19 pandemic; Cessation of life; Clinical; Coronavirus; Data; Development; Disease; Disease Outcome; Dose; Europe; Human; Humoral Immunities; Immune; Immunity; Immunologics; Individual; Infection; Infection Control; Institution; Intervention; Israel; Kinetics; Knowledge; Macaca mulatta; Mediating; Medical center; Phase; Population; Proteins; Resolution; Schedule; Science; Serological; Therapeutic; United States; Vaccinated; Vaccination; Vaccine Clinical Trial; Vaccines; antigen binding; efficacy testing; follow-up; insight; neutralizing antibody; nonhuman primate; prevent; success; transmission process; vaccine development; vector-based vaccine; virology

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.

抽象的 SARS-CoV-2 疫苗的开发可能对于结束 COVID-19 大流行至关重要。然而，一个 知识上的关键差距是缺乏对人类 SARS-CoV-2 免疫相关性的了解。 我们的初步数据表明，抗体与非人类疫苗接种后的保护相关 灵长类动物和独特的抗体功能谱似乎可以预测自然感染中的疾病结果 人类。我们的数据还表明抗体谱趋同，包括抗原结合域驱动 中和作用和 Fc 介导的效应功能驱动保护性免疫。另一个知识缺口是 人类感染 SARS-CoV-2 并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，人类感染 SARS-CoV-2 后抗体滴度可能会迅速下降， 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。 我们假设恢复期和接种疫苗的人类都会产生功能性抗体 与恒河猴针对 SARS-CoV-2 攻击的疫苗保护相关的特征。 我们进一步假设疫苗接种将诱导产生比诱导的抗体更持久的抗体 通过自然感染，可以定义耐久性的免疫相关性。 具体目标 1. 定义 SARS-CoV-2 感染或疫苗接种后相关的抗体谱 有保护。我们将剖析 SARS-CoV-2 感染者引发的功能性抗体反应 以及在 SARS-CoV-2 疫苗接种者中提供对保护相关性的深入了解。 具体目标 2. 定义 SARS-CoV-2 抗体反应持久性的免疫学相关性 感染或接种疫苗后。我们将比较 SARS 中诱导的抗体反应的持久性 CoV-2 感染并接种疫苗的个体，我们将定义持久性的免疫相关性。