Successful treatment of pneumonic
infection with Francisella tularensis, the causative agent of
tularemia, requires rapid initiation of
antibiotic therapy, yet even then treatment failures may occur. Consequently, new treatments are needed to enhance the effectiveness of antimicrobial
therapy for acute pneumonic
tularemia. In a prior study, immunization with F. tularensis
membrane protein fraction (MPF)
antigens 3 days prior to challenge was reported to induce significant protection from inhalational challenge. We therefore hypothesized that MPF immunization might also be effective in enhancing infection control if combined with
antibiotic therapy and administered after
infection as post-exposure
immunotherapy. To address this question, a 24h post-exposure treatment model of acute pulmonary Schu S4 strain of F. tularensis
infection in BALB/c mice was used. Following exposure, mice were immunized with MPF and treated with low-dose
gentamicin, alone or in combination and the effects on survival, bacterial burden and dissemination were assessed. We found that immunization with MPF significantly increased the effectiveness of subtherapeutic
gentamicin for post-exposure treatment of pneumonic
tularemia, with 100% of combination-treated mice surviving long-term. Bacterial burdens in the liver and spleen were significantly reduced in combination MPF-
gentamicin treated mice at 7 days after challenge. Passively transferred
antibodies against MPF
antigens also increased the effectiveness of
gentamicin therapy. Thus, we concluded that post-exposure immunization with MPF
antigens was an effective means of enhancing conventional antimicrobial
therapy for pneumonic
tularemia.