Mycobacterial genes down-regulated during latency

Details Mycobacterial genes down-regulated during latency Mycobacterial genes down-regulated during latency

C - Chemistry, Metallurgy

12

N

C12N 15/31 (2006.01) A61K 31/7088 (2006.01) A61K 35/74 (2006.01) A61K 38/16 (2006.01) A61K 39/04 (2006.01) A61K 39/395 (2006.01) A61K 39/40 (2006.01) A61K 48/00 (2006.01) A61P 31/06 (2006.01) C07K 14/35 (2006.01) C07K 16/12 (2006.01) C12N 1/20 (2006.01) C12N 1/21 (2006.01) C12N 9/00 (2006.01) C12Q 1/02 (2006.01) C12Q 1/68 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2470197

A method is provided for identifying mycobacterial genes the expression of which is down-regulated during a stationary phase culture of mycobacteria under nutrient-starving conditions when compared with an exponential phase culture of mycobacteria under culture conditions that are not nutrient- starving and that support exponential growth of said mycobacteria. The described method optionally provides for identifying mycobacterial genes that are simultaneously down-regulated under low DOT conditions. The down-regulated genes of the present invention form the basis of nucleic acid vaccines, or provide targets to allow preparation of attenuated mycobacteria for vaccines against mycobacterial infections. Similarly, peptides encoded by said down- regulated genes are employed in vaccines. In a further embodiment, the identified genes/peptides provide the means for identifying the presence of a mycobacterial infection in a clinical sample by nucleic acid probe or antibody detection.

L'invention se rapporte à un procédé d'identification de gènes mycobactériens dont l'expression est rétro-régulée au cours d'une culture à phase stationnaire de mycobactéries dans des conditions de privation de nutriments par rapport à une culture à phase exponentielle de mycobactéries dans des conditions de culture qui ne sont pas des conditions de privation de nutriments et qui supportent une croissance exponentielle desdites bactéries. Le procédé selon l'invention permet facultativement l'identification de gènes mycobactériens qui sont simultanément rétro-régulés dans des conditions de faible DOT. Les gènes rétro-régulés selon l'invention servent de base aux vaccins à base d'acide nucléique, ou servent de cibles afin de permettre la préparation de mycobactéries atténuées pour des vaccins contre des infections mycobactériennes. Des peptides codés par ces gènes rétro-régulés sont employés de manière identique dans des vaccins. Dans un autre mode de réalisation selon l'invention, les gènes/peptides identifiés fournissent des méthodes d'identification d'une infection mycobactérienne dans un échantillon clinique au moyen d'une sonde d'acide nucléique ou de la détection d'anticorps.

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