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Roles of Antibody in Vaccine-Elicited Protection Against Virulent Francisella tularensis Aerosolized Infection

Olsen, Emily (2020) Roles of Antibody in Vaccine-Elicited Protection Against Virulent Francisella tularensis Aerosolized Infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Olsen, EmilyELO22@pitt.eduelo22
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorReed, Dougdsreed@pitt.edu
Committee MemberMattila, Joshjmattila@pitt.edu
Committee MemberBarratt Boyes, Simonsmbb@pitt.edu
Date: 30 July 2020
Date Type: Publication
Defense Date: 1 April 2020
Approval Date: 30 July 2020
Submission Date: 31 March 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 81
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: tularemia, Francisella, antibody, aerosol
Date Deposited: 30 Jul 2020 19:10
Last Modified: 30 Jul 2020 20:34
URI: http://d-scholarship.pitt.edu/id/eprint/38478

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