Utilization of Francisella tularensis LVS to Generate a Plague/ Tularemia Vaccine

Abstract

Francisella tularensis and Yersinia pestis are bacteria that are classified as potential bioterrorism agents by the Centers for Disease Control and Prevention.  A vaccine that can produce a protective immunity against multiple agents of bioterror would be especially desirable.  Therefore, the overall goal of this research is to create a vaccine that will produce immunity to both Y. pestis and F. tularensis.  We generated a construct in which the coding region for Tul4 (an immunodominant protein of F. tularensis) is linked to OmpA (a protective antigen of Y. pestis) under the control of a robust F. tularensis promoter.  This construct was constructed in E. coli and was subsequently mobilized to F. tularensis LVS (Live Vaccine Strain).  Patients who have been immunized with LVS show an immunological memory of over three decades post-vaccination, so we predict that a similarly lengthy response will be exhibited against the Y. pestis antigen.  The expression of the chimeric Tul4-OmpA protein is currently being verified through western blotting.   After confirmation, mice will be immunized with this recombinant LVS strain then subsequently challenged with both F. tularensis and Y. pestis to determine the efficacy of the recombinant vaccine.  This research will provide information on how to protect against two possible bioterror agents and may even be applied to other bacteria. (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence and a grant from the NASA WV Space Grant Consortium [NNX10AK62H])