Mice sublethally infected with Francisella novicida U112 develop only marginal protective immunity against systemic or aerosol challenge with virulent type A or B strains of F. tularensis

The current study determined the ability of Francisella novicida to act as a live vaccine against the much more virulent, but closely related pathogen, Francisella tularensis. Live attenuated strains of the latter are effective vaccines against human tularemia. However, the molecular cause of their attenuation remains unknown, and this is a regulatory barrier for licensing such vaccines. Moreover, F. tularensis is exceptionally difficult to manipulate genetically. This is hampering the development of rationally attenuated vaccine strains. F. novicida shares a lot of genetic homology with F. tularensis and is more amenable to genetic manipulation. If the former naturally expresses the protective antigens of the latter, it could be used to develop a defined tularemia vaccine. However, the results presented herein show that wild-type F. novicida elicits almost no protection in mice against challenge with virulent F. tularensis.