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AssigneeInstitut Pasteur
InventorsStewart Cole, Alexander S. Pym, Roland Brosch, Priscille Brodin, Laleh Majlessi, Caroline Demangel, Claude LeClerc
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The present invention relates to a strain of M. bovis BCG or M. microti, wherein said strain has integrated part or all of the RD1 region responsible for enhanced immunogenicity of the tubercle bacilli, especially the ESAT-6 and CFP-10 genes. These strains will be referred as the M. bovis BCG::RD1 or M. microti::RD1 strains and are useful as a new improved vaccine for preventing tuberculosis and as a therapeutical product enhancing the stimulation of the immune system for the treatment of bladder cancer.
A strain of M. bovis BCG or M. microti, wherein said strain has integrated all or part of the fragment, named RD1-2F9, of 31808 pb of DNA originating from Mycobacterium tuberculosis or any virulent member of the Mycobacterium tuberculosis complex (M. africanum, M. bovis, M. canetti), as shown in SEQ ID No 1 and which is responsible for enhanced immunogenicity and increased persistence of BCG to the tubercle bacilli.
M. bovis BCG::RD1 strains which have integrated a cosmid herein referred to as RD1-2F9 and RD1-AP34 contained in the E. coli strains deposited at the CNCM under the accession number 1-2831 and 1-2832 respectively.
M. bovis BCG::RD1 strain which has integrated the insert of the cosmid RD1-AP34 which corresponds to the 3909 bp fragment of the M. tuberculosis H37Rv genome from region 4350459 bp to 4354367 bp cloned as shown in SEQ ID No 3.
M. bovis BCG::RD1 strain which has integrated the insert of the cosmid RD1-2F9 (˜32 kb) that covers the region of the M. tuberculosis genome AL123456 from ca 4337 kb to ca. 4369 kb as shown in SEQ ID No 1.
M. microti::RD1 strain which has integrated the insert of the cosmid RD1-AP34 which corresponds to the 3909 bp fragment of the M. tuberculosis H37Rv genome from region 4350459 bp to 4354367 bp cloned as shown in SEQ ID No 3).
M. microti::RD1 strain which has integrated the insert of the cosmid RD1-2F9 (˜32 kb) that covers the region of the M. tuberculosis genome AL123456 from ca 4337 kb to ca. 4369 kb as shown in SEQ ID No 1.
A cosmid or a plasmid comprising a portion of DNA originating from Mycobacterium tuberculosis or any virulent member of the Mycobacterium tuberculosis complex (M. africanum, M. bovis, M. canettii), said portion of DNA comprising at least one, two, three or more gene(s) selected from Rv3861 (SEQ ID No 4), Rv3862 (SEQ ID No 5);
A cosmid or a plasmid comprising a portion of DNA originating from Mycobacterium tuberculosis or any virulent member of the Mycobacterium tuberculosis complex (M. africanum, M. bovis, M. canettii), said portion of DNA comprising at least one, two, three or more gene(s) selected from Rv3867 (SEQ ID No 10), Rv3868 (SEQ ID No 11);
A cosmid or a plasmid comprising a portion of DNA originating from Mycobacterium tuberculosis or any virulent member of the Mycobacterium tuberculosis complex (M. africanum, M. bovis, M. conettii), said portion of DNA comprising at least one gene selected from Rv3871 (SEQ ID No 14), Rv3872 (SEQ ID No 15, mycobacterial PE), Rv3873 (SEQ ID No 16, PPE), Rv3874 (SEQ ID No 17, CFP-10), Rv3875 (SEQ ID No 18, ESAT-6) and Rv3876 (SEQ ID No 12).
A cosmid herein referred as RD1-2F9 and RD1-AP34 contained in the E. coli strains deposited at the CNCM under the accession number 1-2831 and 1-2832 respectively.
A method for the identification at the species level of members of the M. tuberculosis complex by means of markers for RD1mic and RD5mic as molecular diagnostic test.
A diagnostic kit for the identification at the species level of members of the M. tuberculosis complex comprising DNA probes and primers specifically hybridizing to a DNA portion of the RD1 or RD5 region of M. tuberculosis, more particularly probes hybridizing under stringent conditions to a gene selected from Rv3871 (SEQ ID No 14), Rv3872 (SEQ ID No 15, mycobacterial PE), Rv3873 (SEQ ID No 16, PPE), Rv3874 (SEQ ID No 17, CFP-10), Rv3875 (SEQ ID No 18, ESAT-6), Rv3876 (SEQ ID No 19) and Rv3877 (SEQ ID No 20), preferably CFP-10 and ESAT-6.
A diagnostic kit for the identification at the species level of members of the M. tuberculosis complex comprising at least one, two, three or more antibodies directed to mycobacterial PE, PPE, CFP-10, ESAT-6.
Virulence markers associated with RD1 and/or RD5 regions of the genome of M. tuberculosis or a part of these regions.
Dependencies are inferred from the claim text.