151. Aerosol prime-boost vaccination provides strong protection in outbred rabbits against virulent type A Francisella tularensis
- Subjects
Physiology ,Fevers ,Pathology and Laboratory Medicine ,Biochemistry ,Immune Physiology ,Medicine and Health Sciences ,Public and Occupational Health ,Francisella ,Enzyme-Linked Immunoassays ,Francisella tularensis ,Materials ,Tularemia ,Mammals ,Vaccines ,Immune System Proteins ,Virulence ,Vaccination ,Eukaryota ,Animal Models ,Vaccination and Immunization ,Antibodies, Bacterial ,Bacterial Pathogens ,Infectious Diseases ,Experimental Organism Systems ,Medical Microbiology ,Vertebrates ,Physical Sciences ,Bacterial Vaccines ,Leporids ,Rabbits ,Pathogens ,Research Article ,Infectious Disease Control ,Materials Science ,Immunology ,Dose-Response Relationship, Immunologic ,Immunization, Secondary ,Blood Sedimentation ,Research and Analysis Methods ,complex mixtures ,Microbiology ,Antibodies ,Signs and Symptoms ,Diagnostic Medicine ,Weight Loss ,Animals, Outbred Strains ,Animals ,Immunoassays ,Microbial Pathogens ,Aerosols ,Bacteria ,Organisms ,Biology and Life Sciences ,Proteins ,Correction ,Survival Analysis ,Mixtures ,Immunoglobulin G ,Amniotes ,Animal Studies ,Immunologic Techniques ,Preventive Medicine - Abstract
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 S4ΔaroD offers significant protection (83% survival) in an outbred animal model, New Zealand White rabbits, against aerosol challenge with 248 cfu (11 LD50) 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 LD50), protection was still good with 66% of S4ΔaroD-vaccinated rabbits surviving while 50% of S4ΔguaBA 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.
- Published
- 2018