Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens.
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.
Brodin
Priscille
P
Unités de Génétique Moléculaire Bactérienne, INSERM E0352, Institut Pasteur, Paris, France.
Majlessi
Laleh
L
Brosch
Roland
R
Smith
Debbie
D
Bancroft
Gregory
G
Clark
Simon
S
Williams
Ann
A
Leclerc
Claude
C
Cole
Stewart T
ST
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
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