Biomedical Sciences ETDs

Publication Date

Summer 7-15-2020

Abstract

Staphylococcus aureus is a pathogenic bacterium that inflicts a large amount of human suffering using an arsenal of virulence factors to cause minor to life-threatening infections. Both the accessory gene regulator (agr) operon, a virulence regulatory pathway that controls expression of over 200 virulence factors, and alpha-hemolysin (Hla), a key pore-forming toxin, play a significant role in infection severity. Given the clinical trial failures of S. aureus vaccine candidates and the prevalence of antibiotic-resistant strains, novel and effective treatment options are urgently needed. Chapter 2 describes a novel virus-like particle (VLP) -based vaccine inducing agr-I-inhibiting antibodies and reducing infection severity in vivo. Chapter 3 describes two novel VLP-based vaccines inducing Hla-neutralizing antibodies targeting a linear neutralizing domain, reducing Hla-mediated pathogenesis during in vivo toxin challenge. These vaccines significantly add to the tool belt of effective S. aureus virulence inhibitors and may help address the antimicrobial resistance crisis.

Keywords

Staphylococcus aureus, virus-like particle, vaccine, virulence factors

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Pamela Hall

Second Committee Member

Aaron Neumann

Third Committee Member

Bryce Chackerian

Fourth Committee Member

David Peabody

Fifth Committee Member

Pavan Muttil

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