Abstract
The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG::RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.
| Original language | English |
|---|---|
| Pages (from-to) | 533-539 |
| Number of pages | 7 |
| Journal | Nature Medicine |
| Volume | 9 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 May 2003 |
Bibliographical note
Funding Information:Acknowledgments We thank P. Chavarot, S.V. Gordon, M. Huerre, H. Khun, E. Maranghi, M. Marmiesse, P. Sebo and D. van Soolingen for advice, support, reagents and sharing of data. This work was funded by the Wellcome Trust, the Institut Pasteur (PTR110), the European Community (QLK2-CT1999-01093) and the Association Française Raoul Follereau. A.S.P. has a Wellcome Trust Training Fellowship in Clinical Tropical Medicine. This paper is dedicated to the memory of M.J. Colston.
