title: Room temperature stabilization of oral, live attenuated Salmonella enterica serovar Typhi-vectored vaccines.
abstract: Foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated Salmonella Typhi 'Ty21a' bacterial vaccine. Ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. Growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. The optimized Ty21a vaccine, formulated with trehalose, methionine, and gelatin, demonstrated stability for approximately 12 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1log(10)CFU) and no loss in titer at 4 and 25°C following storage for the same duration. Furthermore, the foam dried Ty21a elicited a similar immunogenic response in mice as well as protection in challenge studies compared to Vivotif™, the commercial Ty21a vaccine. The enhanced heat stability of the Ty21a oral vaccine, or Ty21a derivatives expressing foreign antigens (e.g. anthrax), could mitigate risks of vaccine potency loss during long-term storage, shipping, delivery to geographical areas with warmer climates or during emergency distribution following a bioterrorist attack. Because the foam drying process is conducted using conventional freeze dryers and can be readily implemented at any freeze drying manufacturing facility, this technology appears ready and appropriate for large scale processing of foam dried vaccines.
authors.affiliation: Aridis Pharmaceuticals, San Jose, CA 95138, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtake
authors.forename: Russell
authors.initials: R
authors.lastname: Martin
authors.forename: Atul
authors.initials: A
authors.lastname: Saxena
authors.forename: Binh
authors.initials: B
authors.lastname: Pham
authors.forename: Gary
authors.initials: G
authors.lastname: Chiueh
authors.forename: Manuel
authors.initials: M
authors.lastname: Osorio
authors.forename: Dennis
authors.initials: D
authors.lastname: Kopecko
authors.forename: Deqi
authors.initials: D
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Lechuga-Ballesteros
authors.forename: Vu
authors.initials: V
authors.lastname: Truong-Le
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D004337:Drug Carriers; D004355:Drug Stability; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D050296:Microbial Viability / Q000528:radiation effects*; D012485:Salmonella typhi / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D013696:Temperature; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D004337:Drug Carriers; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic