Progress, challenges, and opportunities in Francisella vaccine development

ABSTRACT

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.

KEYWORDS:

• Francisella tularensis
• tularemia
• protective immunity
• correlates
• intracellular bacteria
• T cells
• vaccines

Acknowledgements

We thank our collaborators on the studies described here, particularly Francis Nano, Wayne Conlan, Anders Sjöstedt, Patrik Rydén, and Terry Wu, for productive and enjoyable interactions across many years of work. We further thank our colleagues Freyja Lynn, Steven Derrick, and Theresa Finn, and other members of OVRR/CBER, for their thoughtful, careful review of this manuscript and invaluable discussions.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Disclaimer

This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.