Biomedical Sciences ETDs

Author

Erin Crossey

Publication Date

5-1-2016

Abstract

Virus-like particles (VLPs) make excellent vaccines. They are non-infectious, often easy to produce in bacterial expression systems, and highly immunogenic. The latter feature is granted by the regularity of the capsid structure, which presents viral (or other) epitopes as dense, highly repetitive arrays that strongly stimulate B cells. VLPs can be used as the basis for vaccines targeting the virus from which they were derived, or they can be used as platforms to display practically any short peptide epitope in a multivalent format. Foreign peptides displayed on VLPs exhibit the same high immunogenicity as unmodified VLPs. Even self-antigens, normally subject to the mechanisms of B cell tolerance, are immunogenic when displayed at high density on the surface of VLPs. Several VLP-based vaccines that target heterologous foreign antigens derived from pathogens and self-antigens involved in disease are currently in clinical trials. As a powerful tool for vaccine development and discovery, we have applied VLP strategies in two different studies. We first generated a VLP vaccine targeting a self-antigen involved in cholesterol metabolism (PCSK9) that has exciting potential as a lipid-lowering agent. We next utilized VLPs in an affinity selection strategy to identify potential vaccine candidates that target a highly conserved malaria parasite target (AMA1) and have identified at least one VLP that elicits a relevant immune response. Through these studies we have expanded the applications for VLPs and further characterized methods for vaccine discovery for myriad targets in the future.

Keywords

virus-like particle, bacteriophage, affinity selection, vaccine, malaria, hypercholesterolemia

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Chackerian, Bryce

First Committee Member (Chair)

Peabody, David

Second Committee Member

Hjelle, Brian

Third Committee Member

Ozbun, Michelle

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