Researcher ORCID Identifier

0000-0002-9681-9082

Graduation Year

2022

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Biology

Reader 1

Dr. Gene S. Tan

Reader 2

Dr. Anna G. Wenzel

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Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© 2021 Benjamin L Sievers

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the virus responsible for the ongoing COVID-19 pandemic and the cause of over 5 million deaths worldwide. Remarkably and for reasons that are not yet clear, COVID-19 severity ranges from asymptomatic infections to multi-stage organ failure and death. As evidenced from the Middle East respiratory syndrome (MERS) virus and severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), CoV-encoded accessory proteins play critical roles in immune response and host-virus interactions. Previous studies investigating the ORF3a protein of SARS-CoV-1 demonstrated that SARS-CoV-1 specific ORF3a antibodies can neutralize virus in animal models and elicit potentially protective humoral and cell-based immune responses in infected patients. Prior immune responses to ORF3-like proteins from related coronaviruses might play a critical role in the modulation of disease severity and viral clearance when an individual is newly exposed to SARS-CoV-2. We found that SARS-CoV-2 ORF3a antibody titers among SARS-CoV-2 infected patients were significantly lower among COVID-19 patients with severe disease and comparatively higher among those with more mild disease manifestations. The observation of unusually high titers of ORF3a antibodies among children with documented SARS-CoV-2 by PCR is reminiscent of antibody responses following booster vaccinations. It is highly suggestive that these high titers represent an anamnestic response to prior endemic coronavirus infections. It is therefore conceivable that ORF3a-related memory B-cell responses associated with prior endemic coronavirus infections might be somewhat protective in the setting of de novo SARS-CoV-2 infections. While formal causality cannot be established, these findings suggest that ORF3a humoral responses might also meaningfully contribute to effective and protective cell-mediated immunity. With the continued global development of SARS-CoV-2 variants of concern that may evade conventional spike-targeted vaccine strategies, the ORF3a protein represents a promising antigen for consideration in the development of novel multivalent coronavirus vaccines.

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