title: Elimination of the cold-chain dependence of a nanoemulsion adjuvanted vaccine against tuberculosis by lyophilization.
abstract: Next-generation rationally-designed vaccine adjuvants represent a significant breakthrough to enable development of vaccines against challenging diseases including tuberculosis, HIV, and malaria. New vaccine candidates often require maintenance of a cold-chain process to ensure long-term stability and separate vials to enable bedside mixing of antigen and adjuvant. This presents a significant financial and technological barrier to worldwide implementation of such vaccines. Herein we describe the development and characterization of a tuberculosis vaccine comprised of both antigen and adjuvant components that are stable in a single vial at sustained elevated temperatures. Further this vaccine retains the ability to elicit both antibody and TH1 responses against the vaccine antigen and protect against experimental challenge with Mycobacterium tuberculosis. These results represent a significant breakthrough in the development of vaccine candidates that can be implemented throughout the world without being hampered by the necessity of a continuous cold chain or separate adjuvant and antigen vials.
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA. Electronic address: mark.orr@idri.org.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Orr
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Kramer
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Lucien
authors.initials: L
authors.lastname: Barnes
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Quinton M
authors.initials: QM
authors.lastname: Dowling
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Desbien
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Elyse A
authors.initials: EA
authors.lastname: Beebe
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Laurance
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Vedvick
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology; D058491:Bacterial Load; D004655:Emulsions; D005260:Female; D005612:Freeze Drying; D007958:Leukocyte Count; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D013696:Temperature; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004655:Emulsions; D032581:Tuberculosis Vaccines
keywords: Adjuvant; Lyophilization; Nanoemulsion; Vaccine