Development of a Novel Francisella tularensis SCHU S4 htpG Deletion Mutant
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Author/Creator ORCID
Date
2020-04-28
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Department
Hood College Biology
Program
Hood College Biomedical and Environmental Science
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Attribution 3.0 United States
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Abstract
Development of a live attenuated vaccine for F. tularensis has been challenged by the difficulty of balancing attenuation with efficacy. To date, all vaccine candidates have failed to achieve licensure due to residual virulence and non-optimal protection against pneumonic tularemia, leaving a gap in biopreparedness. One recent mutant of F. tularensis subsp. tularensis SCHU S4 with a deletion of the clpB gene has been shown to be a highly attenuated and effective vaccine but attempts to add additional attenuating deletions have resulted in loss of efficacy. The need for additional attenuation may be required for licensure. Therefore, there is a critical need to identify other SCHU S4 mutants which may share similar properties to SCHU S4 ΔclpB and may be more permitting of additional attenuation. We propose development and characterization of a SCHU S4 ΔhtpG mutant in vitro and in vivo in BALB/c mice for safety and efficacy upon aerosol challenge by the virulent SCHU S4 strain. In addition, we propose to assess course of infection upon administration and molecular immune responses to determine if SCHU S4 ΔhtpG may present a unique opportunity to develop a new tularemia vaccine platform which is more permitting of additional attenuating deletions.