Abstract Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent bacterial pathogen and the causative agent of tularemia. There are no licensed tularemia vaccines and experimental live vaccine strains (LVS) vary in their protective efficacy and are poorly defined. Development of novel vaccines will require improvement of protection over the existing LVS and preferably incorporation of well-defined epitopes. However, protective epitopes for tularemia have not been identified. Surviving tularemia requires a strong polyfunctional CD4+ T cell response. Due to the importance of the CD4+ T cell response, we hypothesized ectopic expression of an epitope recognized by high avidity CD4+ T cells would enhance existing vaccine efficacy, regardless of the epitope’s origin. gp61 and LLO are well characterized CD4+ T cell epitopes derived from LCMV and Listeria, respectively, and are recognized by C57Bl/6, but not Balb/c mice. Expression of gp61 or LLO during primary infection with LVS or Ftt improved survival of C57Bl/6, but not Balb/c mice, indicating the presence of low numbers of high avidity CD4+ precursor T cells alters survival during Francisella infection. Furthermore, mice vaccinated with LVS gp61 had significantly improved survival during low and high dose secondary Ftt infection and decreased bacterial burdens compared to controls. Together, this demonstrates that improved efficacy of current tularemia vaccine platforms is achieved by properly targeting appropriate antigen-specific cellular responses. Moreover, the elucidation of Francisella epitopes that elicit high-avidity CD4+ T cell responses, specifically in humans, will be required for successful vaccine development.