Biomedical Sciences ETDs

Publication Date

Summer 7-8-2024

Abstract

Virus-like particles (VLPs) are nanoparticles comprised of viral structural proteins. They physically resemble the virus from which they are derived but lack genomic material. They are non-infectious, non-replicating, and have a favorable safety profile. VLPs are highly immunogenic with a dense, repetitive structure that is strongly activating for B cells. VLPs can be utilized to develop vaccines and can be used either as direct immunogens or platforms for the display of heterologous antigens. The display of foreign peptides on VLPs can be used to elicit high-titer antibodies against the displayed peptide. A virus-like particle based on the RNA bacteriophage MS2 has been engineered to be highly tolerant of insertions at a surface-exposed site, with implications for epitope discovery and vaccine development. We have produced vast libraries of MS2 VLPs displaying a large number of random or defined epitopes and utilized these libraries for affinity selection and deep sequence-coupled biopanning. We employed an affinity selection paradigm using engineered, chimeric antibodies to identify peptides capable of activating germline precursor B cells with applications for the development of an HIV vaccine. Additionally, we utilized these techniques to interrogate the antibody repertoires generated by patients following natural infection with SARS-CoV-2 and Sin Nombre Virus. We further examined the ability of naturally immunogenic epitopes displayed on MS2 bacteriophage VLPs to generate protective antibodies against these pathogens in animal models or cell culture as available.

Keywords

Virus-like particle, MS2, Deep sequence-coupled biopanning

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Kathryn Frietze

Second Committee Member

Bryce Chackerian

Third Committee Member

Steven Bradfute

Fourth Committee Member

Alison Kell

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