Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Microbiology and Immunology

Supervisor(s)

Dr. John McCormick

Abstract

Streptococcus pyogenes is a human-specific pathogen that is responsible for serious morbidity and mortality worldwide despite being susceptible to common antibiotics. Furthermore, there is currently no licensed vaccine available against this organism. Previous research from our laboratory implicated a critical role for SAgs in a transgenic mouse model of acute nasopharyngeal infection by S. pyogenes. Herein, we are able to detect SAg production in vivo and establish that anti-SAg antibodies generated by either passive immunization or active vaccination with a MHC II-binding interface SAg toxoid reduces S. pyogenes nasopharyngeal burden. We were also able to demonstrate that this organism requires responsive Vβ-specific T cells in order to efficiently infect the upper respiratory tract. These experiments remarkably reveal that S. pyogenes manipulates T cells to promote infection and also supports targeting SAgs as vaccine candidates to prevent nasopharyngeal carrier and subsequent disease caused by this globally important pathogen.

Available for download on Thursday, March 22, 2018


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