title: Formulation and stabilization of Francisella tularensis live vaccine strain.
abstract: Francisella tularensis live vaccine strain (F. tularensis LVS), a promising vaccine candidate for protection against F. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. Our preliminary data show that F. tularensis LVS can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. The process was conducted under mild drying conditions, which resulted in a good titer retention following processing. The inclusion of osmolytes in the growth media resulted in an acceleration of growth kinetics, although no change in osmotolerance was observed. The optimized F. tularensis formulation, which contained trehalose, gelatin, and Pluronic F68 demonstrated stability for approximately 1.5 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1 log(10) colony forming unit) and for 12 weeks at 25°C. At refrigerator storage condition (4°C), stabilized F. tularensis LVS vaccine exhibited no activity loss for at least 12 weeks. This stabilization method utilizes conventional freeze dryers and pharmaceutically approved stabilizers, and thus can be readily implemented at many manufacturing sites for large-scale production of stabilized vaccines. The improved heat stability of the F. tularensis LVS could mitigate risks of vaccine potency loss during long-term storage, shipping, and distribution.
authors.affiliation: Aridis Pharmaceuticals, San Jose, California 95138.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: Aridis Pharmaceuticals, San Jose, California 95138.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Martin
authors.affiliation: Aridis Pharmaceuticals, San Jose, California 95138.
authors.forename: Atul
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Aridis Pharmaceuticals, San Jose, California 95138.
authors.forename: David
authors.initials: D
authors.lastname: Lechuga-Ballesteros
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Araceli E
authors.initials: AE
authors.lastname: Santiago
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Barry
authors.affiliation: Aridis Pharmaceuticals, San Jose, California 95138. Electronic address: truongv@aridispharma.com.
authors.forename: Vu
authors.initials: V
authors.lastname: Truong-Le
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003080:Cold Temperature; D004355:Drug Stability; D004356:Drug Storage; D005604:Francisella tularensis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D005612:Freeze Drying; D006358:Hot Temperature; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology; D014774:Virulence
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated