Biomedical Sciences ETDs

Publication Date

Fall 12-3-2020

Abstract

For filoviruses, a family of hemorrhagic fever viruses, the main antigen for vaccines in development is the glycosylated glycoprotein GP1,2. How the glycosylation of GP1,2 differs when the protein is produced in different cell lines is unclear. We showed significant differences in the types of glycans conferred onto filovirus GP1,2s in produced in mammalian-origin and insect-origin cell lines. Mammalian-derived filovirus GP1,2s have diverse N-linked glycans and extensive O-linked glycans, whereas insect-derived filovirus GP1,2s have N-linked glycans that are primarily paucimannose type and have no observable O-linked glycans. We then showed that differences in glycosylation impacted how immunogenic the proteins were as EBOV vaccines in mice. We found insect-derived GP1,2 elicited higher antibody titers than mammalian-derived GP1,2. We then further demonstrated the importance of viral glycosylation in SARS-CoV-2. SARS-CoV-2 is susceptible to inhibition by iminosugar compounds in vitro. Iminosugars inhibit the early steps of the glycosylation pathway and prevent successful glycoprotein folding.

Keywords

Virus, glycosylation, vaccine, ebola, sars-cov-2

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Steven Bradfute

Second Committee Member

Bryce Chackerian

Third Committee Member

Jennifer Gillette

Fourth Committee Member

Aaron Neumann

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