Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as
tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed
vaccine is currently available for prevention of
tularemia. In this study, we used a novel approach for development of a multivalent
subunit vaccine against
tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent
subunit vaccine was formulated to contain a combination of F. tularensis protective
antigens: OmpA-like
protein (OmpA), chaperone
protein DnaK and
lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different
vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100) doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis
antigens. TMV-
conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis
proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective
antigens of F. tularensis. Refinement of
vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective
tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.