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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Pym AS,Brodin P,Majlessi L,Brosch R,Demangel C,Williams A,Griffiths KE,Marchal G,Leclerc C,Cole STdoi
10.1038/nm859keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
533-9issue
5eissn
1078-8956issn
1546-170Xpii
nm859journal_volume
9pub_type
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