Open AccessAerosol prime-boost vaccination provides strong protection in outbred rabbits against virulent type A Francisella tularensis
Author(s) -
Katherine J. O’Malley,
Jennifer D. Bowling,
Elizabeth Stinson,
Kelly Stefano Cole,
Barbara J. Mann,
Prachi Namjoshi,
Karsten R. O. Hazlett,
Eileen M. Barry,
Douglas S. Reed
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205928
Subject(s) - francisella tularensis , tularemia , vaccination , virulence , attenuated vaccine , virology , biology , microbiology and biotechnology , immunology , antigen , biochemistry , gene
Tularemia, also known as rabbit fever, is a severe zoonotic disease in humans caused by the gram-negative bacterium Francisella tularensis (Ft) . While there have been a number of attempts to develop a vaccine for Ft , few candidates have advanced beyond experiments in inbred mice. We report here that a prime-boost strategy with aerosol delivery of recombinant live attenuated candidate Ft S4Δ aroD offers significant protection (83% survival) in an outbred animal model, New Zealand White rabbits, against aerosol challenge with 248 cfu (11 LD 50 ) of virulent type A Ft SCHU S4. Surviving rabbits given two doses of the attenuated strains by aerosol did not exhibit substantial post-challenge fevers, changes in erythrocyte sedimentation rate or in complete blood counts. At a higher challenge dose (3,186 cfu; 139 LD 50 ), protection was still good with 66% of S4Δ aroD -vaccinated rabbits surviving while 50% of S4Δ guaBA vaccinated rabbits also survived challenge. Pre-challenge plasma IgG titers against Ft SCHU S4 corresponded with survival time after challenge. Western blot analysis found that plasma antibody shifted from predominantly targeting Ft O-antigen after the prime vaccination to other antigens after the boost. These results demonstrate the superior protection conferred by a live attenuated derivative of virulent F . tularensis , particularly when given in an aerosol prime-boost regimen.