A mouse model for tularemia

In this recent paper co-authored by a large group of Researchers at the Department of microbiology and immunolgy, UTMB, Galveston, it is demonstrated for the first time that mice infected via intranasal challenge with virulent Francisella tularensis strain SCHU S4 and then treated with levofloxacin developed protective immunity against subsequent lethal intranasal challenge with SCHU S4. Furthermore, sera from these protected mice was shown to be protective when passively transferred to normal, naive, mice. The full paper can be found at the site of the Journal VACCINE.

The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis.

This mouse model could be helpful in identifying F. tularensis antigens that elicit the formation of protective antibodies. The model might also yield valuable insight into a number of questions still unanswered with regard to protective immunity against inhalation infection with virulent Francisella.