title: Protection elicited by a double leucine and pantothenate auxotroph of Mycobacterium tuberculosis in guinea pigs.
abstract: We developed a live, fully attenuated Mycobacterium tuberculosis vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. The deltaleuD deltapanCD double auxotroph is fully attenuated in the SCID mouse model and highly immunogenic and protective in the extremely sensitive guinea pig tuberculosis model, reducing both bacterial burden and disease pathology.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Sampson
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dascher
authors.forename: Vasan K
authors.initials: VK
authors.lastname: Sambandamurthy
authors.forename: Robert G
authors.initials: RG
authors.lastname: Russell
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Barry R
authors.initials: BR
authors.lastname: Bloom
authors.forename: Mary K
authors.initials: MK
authors.lastname: Hondalus
mesh_terms: D000818:Animals; D005260:Female; D005798:Genes, Bacterial; D006168:Guinea Pigs; D007930:Leucine / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010205:Pantothenic Acid / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000494:pharmacology
chemical_list: D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D010205:Pantothenic Acid; D007930:Leucine