Date of Award

8-22-2024

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

First Advisor

Susan Uprichard

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped beta coronavirus responsible for the coronavirus disease 2019 (CoVID-19) pandemic. While vaccination has been critical in curtailing the pandemic and numerous publications have assessed vaccine response, there are still unanswered questions regarding antibody durability. While it is clear that anti-Spike antibody levels decline relatively quickly in most people after vaccination and infection necessitating the administration of vaccine booster doses, it is unknown whether repeated vaccine doses, pre-/post-vaccination infection or host factors impact antibody durability. Hence, this thesis analyzed samples and demographic data from our longitudinal SARS-CoV-2 vaccinated cohort to elucidate how infection, repeated vaccination, or the combination of both impact the durability of antibody levels. Serial samples collected post-vaccination/infection at 3 weeks, 3 months, and every 3 months until the next antigen exposure occurred were assayed for SARS- CoV-2 anti-S and anti-N antibodies. A questionnaire given to participants at each sample collection provided demographic information and SARS-CoV-2 vaccination/infection dates. Of the participants in the study, 218 had at least three samples between individual antigen exposure events to allow for accurate antibody kinetic analysis, and the 81 participants with the most kinetics series were assessed for this thesis. Multiple analysis methods and group stratification strategies revealed that antibody durability increased with repeated antigen exposure. However, contrary to conclusions made in the literature, we found no evidence that antigen source (i.e., infection vs. vaccination) had any major impact on this pattern of increasing durability. Importantly, 73% of those who provided a sample after their 4th antigen exposure exhibited an enhanced antibody half- life of over 300 days. Though differences in antibody durability achieved between participants were observed, no host factors were identified that associate with these differences leaving open the question of how to identify the smaller percentage of people who do not achieve this improvement in antibody durability with repeated exposures. In summary, we show for the first time that repeated antigen exposure can lead to enhanced antibody durability, providing evidence that annual SARS-CoV-2 vaccination may be a feasible public health strategy, raising intriguing fundamental immunological questions, and adding to our understanding regarding how vaccine boosters can be employed to enhance immune responses.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Wednesday, August 01, 2029

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