Attenuated negative strand viruses with altered interferon...

A - Human Necessities – 61 – K

Patent

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Details

A61K 39/12 (2006.01) A61K 35/76 (2006.01) A61K 39/145 (2006.01) A61K 39/155 (2006.01) A61K 39/17 (2006.01) A61K 39/205 (2006.01) C07K 14/11 (2006.01) C12N 7/00 (2006.01) C12N 7/04 (2006.01) C12N 15/86 (2006.01)

Patent

CA 2334895

The present invention relates, in general, to attenuated negative-strand RNA viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. The invention also relates to the development and use of IFN- deficient systems for selection of such attenuated viruses. In particular, the invention relates to attenuated influenza viruses having modifications to the NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. The mutant viruses replicate in vivo but demonstrate reduced pathogenicity, and therefore are well suited for live virus vaccines, and pharmaceutical formulations.

L'invention concerne, en général, des virus ARN atténués à brin négatif, possédant une capacité altérée d'antagonisme à la réponse cellulaire d'un interféron (IFN), et l'utilisation de ces virus atténués dans des formulations pharmaceutiques et de vaccins. L'invention concerne également le développement et l'utilisation de systèmes déficients en INF pour sélectionner ces virus atténués. L'invention concerne en particulier des virus atténués de la grippe, présentant des modifications du gène NS1, ce qui réduit ou élimine la capacité du produit génique NSQS1 à s'opposer à la réponse cellulaired'un IFN. Les virus mutants se répliquent in vivo mais présentent une pathogénocité réduite. Ils sont cependant appropriés pour des vaccins antiviraux vivants et des formulations pharmaceutiques.

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