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疫苗的开发对于结束Covid-19的大流行可能至关重要。但是， 知识的关键差距是缺乏对人类SARS-COV-2免疫相关的了解。 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特征似乎可以预测自然感染中疾病的结果 人类。我们的数据还指向收敛的抗体曲线，包括抗原结合域驱动 中和和FC介导的效应子功能驱动保护性免疫。知识的另一个差距是 SARS-COV-2感染和人类疫苗接种后，保护性免疫的耐用性未知。 我们的初步数据表明，抗体滴度可能会在人类的SARS-COV-2感染后迅速减弱， 但是需要更大的研究和更长的随访来定义康复中抗体反应的动力学 个人。此外，疫苗吸收抗体反应的耐用性仍有待确定。 我们假设康复和疫苗接种的人都会发展功能性抗体 与恒河猕猴中的SARS-COV-2挑战有关的疫苗保护相关的签名。 我们进一步假设疫苗接种将诱导耐久性抗体比引起的抗体更大 通过自然感染，可以定义耐用性的免疫学相关性。 特定目标1。定义SARS-COV-2感染或疫苗接种后的抗体曲线 使用保护。我们将剖析SARS-COV-2感染个体引起的功能抗体反应 并在SARS-COV-2接种疫苗中提供有关保护相关性的洞察力。 特定目标2。定义SARS-COV-2抗体反应的耐用性的免疫学相关性 感染或疫苗接种后。我们将比较SARS-诱导的抗体反应的耐用性 COV-2感染和接种疫苗的个体，我们将定义耐用性的免疫学相关性。