Protection elicited by a double leucine and pantothenate auxotroph of Mycobacterium tuberculosis in guinea pigs.
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.
Sampson
Samantha L
SL
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Dascher
Christopher C
CC
Sambandamurthy
Vasan K
VK
Russell
Robert G
RG
Jacobs
William R
WR
Bloom
Barry R
BR
Hondalus
Mary K
MK
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
D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D010205:Pantothenic Acid; D007930:Leucine