A polynucleotide functionally coding for the lhp protein...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/31 (2006.01) A61K 39/04 (2006.01) C07K 14/35 (2006.01) C07K 16/12 (2006.01) C07K 19/00 (2006.01) C12N 1/21 (2006.01) C12N 15/62 (2006.01) C12N 15/74 (2006.01) C12Q 1/68 (2006.01) G01N 33/53 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2296419

The present invention is directed to a polynucleotide carrying a n open reading frame coding for an antigenic polypeptide from Mycobacterium tuberculosis, named lhp, which is placed under the control of its own regulation signals which are functional in mycobacteria, specially in mycobacteria belonging to the Mycobacterium tuberculosis complex and also in fast growing mycobacteria such as Mycobacterium smegmatis. The invention is also directed to the polypeptide LHP encoded by lhp and most preferably to suitable antigenic portions of LHP as well as to oligomeric polypeptides containing more than one unit of LHP or an antigenic portion of LHP. The invention concerns also immunogenic and vaccine compositions containing a polypeptide or an oligomeric polypeptide such as defined above, as well as antibodies directed specifically against such polypeptides that are useful as diagnostic reagents. In another embodiment, the present invention is directed to a polynucleotide carrying the natural regulation signals of lhp which is useful in order to express heterologous proteins in mycobacteria. Finally, the present invention is directed to oligonucleotides comprising at least 12 consecutive nucleotides from the regulation sequence of lhp which are useful as reagents for detecting the presence of Mycobacterium tubercolosis in a biological sample.

La présente invention concerne un polynucléotide portant une phase de lecture ouverte codant pour un polypeptide antigène issu de Mycobacterium tuberculosis et dénommé lhp, qui est placé sous la commande de ses propres signaux de régulation qui sont fonctionnels dans les mycobactéries, particulièrement chez les mycobactéries appartenant au complexe Mycobacterium tuberculosis, mais également chez les mycobactéries à croissance rapide telles que Mycobacterium smegmatis. L'invention concerne également le polypeptide LHP codé par lhp, et de préférence des portions antigènes appropriés du LHP ainsi que des polypeptides oligomères contenant plusieurs unités du LHP ou une portion antigène du LHP. L'invention concerne aussi des compositions immunogènes et vaccinales contenant un polypeptide ou un polypeptide oligomère tel que défini précédemment, ainsi que des anticorps spécifiquement dirigés contre de tels polypeptides et qui conviennent particulièrement comme réactifs de diagnostics. Selon une autre réalisation, l'invention concerne un polynucléotide portant les signaux naturels de régulation du lhp permettant notamment d'exprimer des protéines hétérologues dans les mycobactéries. L'invention concerne enfin des oligonucléotides comprenant au moins 12 nucléotides consécutifs provenant de la séquence de régulation du lhp et qui conviennent particulièrement comme réactifs pour détecter la présence de Mycobacterium tuberculosis dans un échantillon biologique.

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