"Antibody profiling of an elderly cohort after SARS-CoV-2 vaccination a" by Gianna Mirabile

Date of Award

1-1-2023

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (vii, 54 pages) : illustrations (some color)

Dissertation/Thesis Chair

Nicholas Mantis

Committee Members

Linda Styer, Jennifer Yates

Keywords

COVID-19 (Disease), Serology, Immunity, Older people

Subject Categories

Public Health

Abstract

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.

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