Progress, challenges, and opportunities in Francisella vaccine development

Renewed interest in Francisella tularensis has resulted in substantial new information about its pathogenesis and immunology, along with development of useful animal models. While understanding of protective immunity against Francisella remains incomplete, data in both animals and humans suggest that inducing T cell-mediated immunity is crucial for successful vaccination with current candidates such as the Live Vaccine Strain (LVS), with specific antibodies and immune B cells playing supporting roles. Consistent with this idea, recent results indicate that measurements of T cell functions and relative gene expression by immune T cells predict vaccine-induced protection in animal models. Because field trials of new vaccines will be difficult to design, using such measurements to derive potential correlates of protection may be important to bridge between animal efficacy studies and people.