title: A single dose of killed Mycobacterium bovis BCG in a novel class of adjuvant (Novasome) protects guinea pigs from lethal tuberculosis.
abstract: The only vaccine currently available for the prevention of tuberculosis in man is a live attenuated vaccine, bacille Calmette-Guerin (BCG), derived from Mycobacterium bovis. Concerns over the lack of the universal efficacy and safety of BCG have resulted in efforts to develop a new generation of TB vaccines. Historically, killed whole-cell preparations of mycobacteria have been ineffective vaccines. We revisited the potential of killed whole-cell vaccines by comparing their efficacy with live BCG Pasteur in a guinea pig challenge model. BCG Pasteur was inactivated with a low concentration of formalin and showed to be non-viable in culture or severe combined immunodeficient mice. Formalin-inactivated BCG was mixed with non-phospholipid liposome adjuvants (Novasomes) and administered to guinea pigs as a single subcutaneous inoculation. All formulations were well tolerated and one conferred a significant survival advantage against lethal aerogenic challenge with M. bovis.
authors.affiliation: TB Research Group, Veterinary Laboratories Agency Weybridge, Department of Statutory and Exotic Bacteria, New Haw, Addlestone, Surrey KT15 3NB, UK. m.a.chambers@vla.defra.gsi.gov.uk
authors.forename: Mark A
authors.initials: MA
authors.lastname: Chambers
authors.forename: D Craig
authors.initials: DC
authors.lastname: Wright
authors.forename: Joan
authors.initials: J
authors.lastname: Brisker
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.forename: Graham
authors.initials: G
authors.lastname: Hatch
authors.forename: Dolores
authors.initials: D
authors.lastname: Gavier-Widén
authors.forename: Graham
authors.initials: G
authors.lastname: Hall
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marsh
authors.forename: R
authors.initials: R
authors.lastname: Glyn Hewinson
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005557:Formaldehyde; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D008081:Liposomes; D008168:Lung / Q000382:microbiology; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D013154:Spleen / Q000382:microbiology; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D008081:Liposomes; D015164:Vaccines, Inactivated; D005557:Formaldehyde