Development of a novel tool for Francisella tularensis immunology (MUC1P.915)

Abstract

Abstract Tularemia, an acute infection caused by Francisella tularensis, can manifest in various forms. Pulmonary tularemia developed after an aerosol exposure to the bacterium has a high risk of mortality in unvaccinated individuals. Therefore, development of a vaccine is of critcal importance but is hampered by a relative lack of understanding of the protective adaptive immune response. Absence of immunological tools to study protective T cell responses has been one of the key hurdles in establishing the profile of immune responses to F. tularensis. We have developed a novel F. tularensis LVS, which constitutively expresses a vgrG-OVA fusion protein containing the epitopes OVA257-264 and OVA323-339. This will allow researchers to study antigen-specifc T cell responses during infecton by F. tularensis. Robust expression of this construct was confirmed by immunoblot from bacterial lysates. An additional chromosomally-integrated expression construct is also being generated for more stable expression throughout in vivo infections. This new tool will allow us to study the memory response to Francisella vaccinaton in ways previously difficult to do. Inital experiments are underway using OT-I and OT-II transgenic mice to study the pathogen-specifc response to Francisella following vaccinaton by the intradermal and intranasal routes in order to determine the ideal conditons for improving survival after pulmonary challenge, which remains a concern in a potental bioterror atack.