Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis

Fransicella tularensis, the causative agent Of tularemia, is in the top category (Category A) of potential agents of bioterrorism. To develop a safer vaccine against aerosolized F. tularensis, we have employed an attenuated Listeria monocytogenes, which shares with F tularensis an intracellular and extraphagosomal lifestyle, as a delivery vehicle for F. tularensis antigens. We constructed recombinant L. monocytogenes (rLm) vaccines stably expressing seven F. tularensis proteins including IglC (rLm/iglC), and tested their immunogenicity and protective efficacy against lethal E tularensis challenge in mice. Mice immunized intradermally with rLm/iglC developed significant cellular immune responses to F tularensis iglC as evidenced by lymphocyte Proliferation and CD4+ and CD8+ T-cell intracellular expression of interferon gamma. Moreover, mice immunized With rLm/iglC were protected against lethal challenge with F tularensis LVS administered by the intranasal route, a route chosen to mimic airborne infection, and, most importantly, against aerosol challenge with the highly Virulent Type A F tularensis SchuS4 strain. (C) 2008 Elsevier Ltd. All rights reserved.