Author(s)

Aimee L. Cunningham^1,2, M. Neal Guentzel¹, Jieh-Juen Yu¹, Nikita Trivedi¹, Karl E. Klose¹, James P. Chambers¹, Bernard P. Arulanandam^1*

¹South Texas Center for Emerging Infectious Disease and Center for Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, TX, USA.
²Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Francisella tularensis is considered a potential bioterrorism agent due to its low infectious dose, high mortality rate, and ability to be spread via the aerosol route. We characterized the F. tularensis subspecies novicida mutant strain FTN0109 as a potential vaccine candidate against tularemia. This strain, which lacks an outer membrane lipoprotein, is attenuated in vitro and in vivo, as it exhibits reduced replication within murine J774 macrophages and has a pulmonary LD₅₀ in BALB/c and C57BL/6 mice of >10⁵ CFU (compared to WT parental strain U112, LD₅₀ < 10 CFU). Intranasal immunization induced strong cellular responses (IFN-γ and IL-2 in splenocyte recall assays) as well as strong humoral responses. Vaccination with FTN0109 also conferred complete protection in BALB/c mice against subsequent pulmonary challenge with 10 LD₅₀ (60,000 CFU) of the murine virulent Francisella strain LVS. We also have demonstrated partial protection (50%) against the highly human virulent subspecies tularensis strain SCHU S4 (25 LD₅₀, 12,500 CFU) following intratracheal vaccination in the Fischer 344 rat, a second rodent model for tularemia. Overall, our results suggest that FTN0109 serves as a potential putative vaccine candidate against pulmonary tularemia.

Tularemia, F. tularensis, Vaccines, Live Attenuated

Cunningham, A. , Guentzel, M. , Yu, J. , Trivedi, N. , Klose, K. , Chambers, J. and Arulanandam, B. (2015) Vaccination with the Live Attenuated Francisella novicida Mutant FTN0109 Protects against Pulmonary Tularemia. World Journal of Vaccines, 5, 25-36. doi: 10.4236/wjv.2015.51004.