Semester

Spring

Date of Graduation

2021

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Mariette Barbier

Committee Member

Rosana Schafer

Committee Member

Slawomir Lukomski

Committee Member

P. Rocco LaSala

Committee Member

Werner Geldenhuys

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause severe, recurrent, and chronic infections. The pathogen is highly adaptable, and pneumonia caused by it is associated with high morbidity and mortality, especially in individuals with the genetic disorder cystic fibrosis. Antibiotic resistance amongst clinical isolates of P. aeruginosa is steadily increasing, and multi-drug resistant strains are prevalent. There is currently no vaccine available for commercial use against P. aeruginosa. For these reasons, we sought to understand the immunity to P. aeruginosa induced by whole cell vaccination and identify antigens for development of future subunit vaccines. In this dissertation, we tested P. aeruginosa and Bordetella pertussis whole cell immunization in parallel and identified unique correlates of protection for each. We next characterized the cross-protective response induced by B. pertussis whole cell immunization towards P. aeruginosa, in wild-type and CF murine models. We identified that pertussis whole cell immunization was induced production of antibodies which bind two P. aeruginosa proteins: GroEL and OprF. Finally, we expanded our previously tested, iron-acquisition system targeting, peptide-based vaccination model to test three novel antigens: FptA, PhuR, and HasR. Altogether, these data are a valuable next step in formulation of a vaccine for P. aeruginosa that can be further optimized for efficacy and considered for clinical trial testing.

Embargo Reason

Patent Pending

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