title: Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens.
abstract: Mycobacterium microti, the vole bacillus, which was used as a live vaccine against tuberculosis until the 1970s, confers the same protection in humans as does Mycobacterium bovis bacille Calmette-Guerin (BCG). However, because the efficacy of the BCG vaccine varies considerably, we have tried to develop a better vaccine by reintroducing into M. microti the complete region of difference 1 (RD1), which is required for secretion of the potent T cell antigens early secreted antigen target (ESAT)-6 and culture filtrate protein (CFP)-10. The resultant recombinant strain, M. microti OV254::RD1-2F9, induced specific ESAT-6 and CFP-10 immune responses in mice with CD8(+) T lymphocytes that had strong expression of the CD44(hi) activation marker. This vaccine also displayed better efficacy against disseminated disease in the mouse and the guinea pig models of tuberculosis than was seen in animals vaccinated with M. microti alone or with BCG. The M. microti OV254::RD1-2F9 vaccine was less virulent and persistent in mice and than was BCG::RD1-2F9 may represent a safer alternative to BCG::RD1-2F9.
authors.affiliation: Unités de Génétique Moléculaire Bactérienne, INSERM E0352, Institut Pasteur, Paris, France.
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.forename: Debbie
authors.initials: D
authors.lastname: Smith
authors.forename: Gregory
authors.initials: G
authors.lastname: Bancroft
authors.forename: Simon
authors.initials: S
authors.lastname: Clark
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D006168:Guinea Pigs; D018960:Hyaluronan Receptors / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009161:Mycobacterium / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018960:Hyaluronan Receptors; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic