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Antibody Profiling of an Elderly Cohort After SARS-CoV-2 Vaccination and Infection Using Dried Blood Spots

机译:SARS-CoV-2 疫苗接种和使用干血斑感染后老年队列的抗体分析

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摘要

Three years after the emergence of SARS-CoV-2 in Wuhan, China, COVID-19 remains a major public health emergency throughout the globe. Although major advancements have been made in terms of controlling the virus, such as the use of mRNA vaccines, SARS-CoV-2 infections from variants of concern (VoC) continue to persist and cause significant morbidity and mortality in vulnerable populations, including the elderly. The ability for public health entities to effectively gauge disease susceptibility across large swaths of the population is critical in deciding when to implement new vaccination recommendations. Dried blood spots (DBS) are an upcoming serological sample type being studied due to its ease in storage and ability for self-collection, allowing it to be a method to screen susceptible populations in the future. Because of this, it was important to be able to investigate the effectiveness of DBS using various assays to determine how far the limits of DBS could be stretched. The goal of my thesis was to use available DBS to better understand the humoral immune response to SARS-CoV-2 vaccination or natural infection in an elderly population. This includes looking at binding activity and inhibition abilities to determine traits that elicit a desired immune response. We performed serological analysis of an elderly cohort known as ARIC (Atherosclerosis Risk in Communities), which consists of ~1,400 individuals that are primarily in their 80s and 90s. Self-collected DBS from the ARIC were provided to the Wadsworth Center by way of the Collaborative Cohort of Cohorts for COVID-19 Research(C4R). Using various microsphere immunoassays (MIA), we determined that DBS IgG produced in response to SARS-CoV-2 exposure or vaccination interacted highly with RBD on the SARS-CoV-2 spike glycoprotein. RBD-specific antibodies elicited by vaccination interacted with RBD antigens from the SARS-CoV-2 Beta, Delta, and Omicron variant. There was a positive correlation between antibody binding to RBD and inhibition of binding between the virus spike glycoprotein and the ACE2 receptor. Finally, we observed a trend in that antibody quality, which we define as antibodies that prevent viral interaction with ACE2, and quantity are oftentimes unrelated, with antibody quality being of more importance than quantity of antibodies present. We also optimized parameters of DBS analysis and factors that influence assay performance. The current data set was submitted to C4R for the purpose of establishing a relationship between personal attributes such as age, sex, gender, and more with overall SARS-CoV-2 antibody profiles. I conclude that DBS is an effective tool for serological analysis of cohorts and provides insight on the antibody profiles following SARS-CoV-2 exposure.
机译:SARS-CoV-2 在中国武汉出现三年后,COVID-19 仍然是全球的主要突发公共卫生事件。尽管在控制病毒方面取得了重大进展,例如使用 mRNA 疫苗,但由关注变体 (VoC) 引起的 SARS-CoV-2 感染继续存在,并在包括老年人在内的弱势群体中造成严重的发病率和死亡率。公共卫生实体有效衡量大量人口的疾病易感性的能力对于决定何时实施新的疫苗接种建议至关重要。干血斑 (DBS) 是一种即将研究的血清学样本类型,因为它易于储存且能够自行采集,使其成为未来筛查易感人群的一种方法。因此,能够使用各种分析来研究 DBS 的有效性以确定 DBS 的极限可以延伸多远非常重要。我论文的目标是使用可用的 DBS 来更好地了解老年人群对 SARS-CoV-2 疫苗接种或自然感染的体液免疫反应。这包括查看结合活性和抑制能力,以确定引发所需免疫反应的性状。我们对一个名为 ARIC(社区动脉粥样硬化风险)的老年队列进行了血清学分析,该队列由 ~1,400 名主要在 80 多岁和 90 多岁的人组成。从 ARIC 自行收集的 DBS 通过 COVID-19 研究队列协作队列 (C4R) 提供给沃兹沃思中心。使用各种微球免疫测定 (MIA),我们确定响应 SARS-CoV-2 暴露或疫苗接种产生的 DBS IgG 与 SARS-CoV-2 刺突糖蛋白上的 RBD 高度相互作用。疫苗接种引发的 RBD 特异性抗体与 SARS-CoV-2 Beta、Delta 和 Omicron 变体的 RBD 抗原相互作用。抗体与 RBD 的结合与病毒刺突糖蛋白与 ACE2 受体之间的结合抑制之间存在正相关。最后,我们观察到抗体质量的趋势,我们将其定义为阻止病毒与 ACE2 相互作用的抗体,数量通常无关,抗体质量比存在的抗体数量更重要。我们还优化了 DBS 分析的参数和影响分析性能的因素。当前数据集已提交给 C4R,目的是在年龄、性别、性别等个人属性与整体 SARS-CoV-2 抗体谱之间建立关系。我得出的结论是,DBS 是队列血清学分析的有效工具,并提供了有关 SARS-CoV-2 暴露后抗体谱的见解。

著录项

  • 作者

    Mirabile, Gianna M.;

  • 作者单位

    State University of New York at Albany.;

    State University of New York at Albany.;

    State University of New York at Albany.;

  • 授予单位 State University of New York at Albany.;State University of New York at Albany.;State University of New York at Albany.;
  • 学科 Public health.;Immunology.;Biology.
  • 学位
  • 年度 2023
  • 页码 62
  • 总页数 62
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Public health.; Immunology.; Biology.;

    机译:公共卫生。;免疫学。;生物学。;
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