F tularensis is among of the most virulent pathogens known, yet it remains poorly understood. Correlates of protection involve robust CD4+ and CD8+ T cell responses, and the production of IFN-gamma, TNF-alpha, and IL-12. Novel approaches may be required to develop a safe vaccine that achieves these correlates. In contrast to other types of vaccines, epitope-based vaccines combine targeted biologic activity with the practical advantages of platform independence, scalable synthesis and manufacturing. These advantages, coupled with the proof of principle achieved with an epitope-based tularemia vaccine, suggest that this approach might be applied more widely to develop vaccines against other pathogens, intracellular bacteria most notably.