Current status of vaccine development for tularemia preparedness

Abstract

Tularemia is a high-risk infectious disease caused by Gram-negative bacterium Francisella tularensis. Due to its high fatality at very low colony-forming units (less than 10), F. tularensis is considered as a powerful potential bioterrorism agent. Vaccine could be the most efficient way to prevent the citizen from infection of F. tularensis when the bioterrorism happens, but officially approved vaccine with both efficacy and safety is not developed yet. Research for the development of tularemia vaccine has been focusing on the live attenuated vaccine strain (LVS) for long history, still there are no LVS confirmed for the safety which should be an essential factor for general vaccination program. Furthermore the LVS did not show protection efficacy against high-risk subspecies tularensis (type A) as high as the level against subspecies holarctica (type B) in human. Though the subunit or recombinant vaccine candidates have been considered for better safety, any results did not show better prevention efficacy than the LVS candidate against F. tularensis infection. Currently there are some more trials to develop vaccine using mutant strains or nonpathogenic F. novicida strain, but it did not reveal effective candidates overwhelming the LVS either. Difference in the protection efficacy of LVS against type A strain in human and the low level protection of many subunit or recombinant vaccine candidates lead the scientists to consider the live vaccine development using type A strain could be ultimate answer for the tularemia vaccine development.

Keywords: Bioterrorism agent; Fracisella tularensis; Preparedness; Tularemia; Vaccines.

Fig. 1

Transmission of Francisella tularensis from wild animals and environments to human. Type A tularemia caused by F. tularensis subsp. tularensis is usually transmitted through the terrestrial route by vectors such as ticks and deer flies while type B tularemia raised by F. tularensis subsp. holarctica and other subspecies is transmitted through both routes of aquatic and terrestrial cycles.

Fig. 2

Survival mechanism of Francisella tularensis in macrophage after infection. Infected bacteria is engulfed by endosome for phagocytic activity, however some bacteria developed the immune escaping capability to develop autophagy instead of phagocytosis. EEA, early endosome antigen; LAMP, lysosome-associated membrane protein.