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.

摘要 SARS-CoV-2疫苗的开发可能对结束COVID-19大流行至关重要。但 知识的关键差距是缺乏对人类SARS-CoV-2免疫相关性的理解。 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。 独特的抗体功能谱似乎可以预测自然感染中的疾病结果， 人类我们的数据还指出了一个收敛的抗体概况，包括抗原结合结构域驱动 中和和Fc介导的效应子功能驱动保护性免疫。知识的另一个缺口是 在人类中SARS-CoV-2感染和接种疫苗后，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，抗体滴度可能迅速下降， 但需要更大规模的研究和更长时间的随访来确定恢复期患者抗体反应的动力学。 个体此外，疫苗引起的抗体应答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 与恒河猴中SARS-CoV-2攻击的疫苗保护相关的特征。 我们进一步假设，疫苗接种将诱导抗体具有更大的持久性比那些诱导 通过自然感染和免疫相关的耐久性可以定义。 具体目标1。定义SARS-CoV-2感染或接种疫苗后的抗体谱， 有保护我们将剖析SARS-CoV-2感染个体中引发的功能性抗体应答 以及SARS-CoV-2疫苗接种个体中的研究，以深入了解保护的相关性。 具体目标2。定义SARS-CoV-2抗体应答持久性的免疫学相关性 感染或接种疫苗后。我们将比较SARS诱导的抗体反应的持久性- 感染CoV-2并接种疫苗的个体，我们将定义持久性的免疫学相关性。