eprintid: 38478
rev_number: 22
userid: 8955
dir: disk0/00/03/84/78
datestamp: 2020-07-30 19:10:34
lastmod: 2020-07-30 20:34:11
status_changed: 2020-07-30 20:34:11
type: thesis_degree
metadata_visibility: show
contact_email: emily.olsen.cooks@gmail.com
eprint_status: archive
creators_name: Olsen, Emily
creators_email: ELO22@pitt.edu
creators_id: elo22
title: Roles of Antibody in Vaccine-Elicited Protection Against Virulent Francisella tularensis Aerosolized Infection
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: tularemia, Francisella, antibody, aerosol
abstract: Francisella tularensis, the causative agent of tularemia, is a facultative intracellular bacterium that infects a wide variety of cell types, most notably phagocytes. Initial studies of F. tularensis focused on using plasma to passively immunize subjects as a mechanism of protection, with varied results. Here, we purified the antibodies from plasma of rabbits that were immunized in a prime-boost schedule of a live attenuated mutant of virulent Ft. tularensis (Schu S4 ΔAroD) infection that also survived challenge from the fully virulent strain. We also examined the ability of the antibodies to opsonize and fix complement to Ft. holarctica Live Vaccine Strain. When BALB/c mice were passively immunized either intraperitoneally or intranasally with our polyclonal antibody solutions there was an extension of time to death in lethal doses, significantly less weight loss in immunized animals, and a slight decrease in bacterial titers within the tissues of animals. These data indicate that while antibodies alone are not a mechanism of protection in the mouse model, they do reduce clinical disease and may play a role in vaccine-mediated protection against aerosolized infection with the Live Vaccine Strain. These findings further warrant future studies in other animal models that recapitulate human disease. These findings contribute to the development of therapeutics for infection, and are significant to public health because of the potential of F. tularensis to be used as a biological weapon.
date: 2020-07-30
date_type: published
pages: 81
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: thesis_advisor
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Reed, Doug
etdcommittee_name: Mattila, Josh
etdcommittee_name: Barratt Boyes, Simon
etdcommittee_email: dsreed@pitt.edu
etdcommittee_email: jmattila@pitt.edu
etdcommittee_email: smbb@pitt.edu
etd_defense_date: 2020-04-01
etd_approval_date: 2020-07-30
etd_submission_date: 2020-03-31
etd_release_date: 2020-07-30
etd_access_restriction: immediate
etd_patent_pending: FALSE
thesis_type: thesis
degree: MS
citation:   Olsen, Emily  (2020) Roles of Antibody in Vaccine-Elicited Protection Against Virulent Francisella tularensis Aerosolized Infection.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/38478/1/OlsenE_MSthesis_April2020final.pdf