Ricin vaccine and methods of making and using thereof

Details Ricin vaccine and methods of making and using thereof Ricin vaccine and methods of making and using thereof

C - Chemistry, Metallurgy

12

Q

C12Q 1/00 (2006.01) A61K 38/43 (2006.01) A61K 38/47 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01) C07H 21/04 (2006.01) C07K 14/415 (2006.01) C12N 9/00 (2006.01) C12N 9/24 (2006.01) C12N 9/26 (2006.01) C12N 9/38 (2006.01)

Patent

CA 2477094

Disclosed herein are polypeptides and variants thereof comprising a polypeptide sequence having substantial identity to ricin A chain (RTA0 that lack detectable N-glycosidase-rRNA activity or exhibit reduced N-glycosidase- rRNA activity as compared to controls and methods of making and using thereof. The polypeptides and variants have a greater solubility in aqueous solutions of physiological pH and ionic strength than RTA and also retain the integretiy of the neutralizing immunological epitope of wild type RTA. Also disclosed are immunogenic compositions that may be used to immunize a subject against ricin intoxication. Methods of immunizing against, treating, and preventing ricin intoxication are disclosed.

L'invention concerne des polypeptides et des variantes de ceux-ci, comprenant une séquence polypeptidique possédant une similitude sensible avec la chaîne A du ricin (RTA), dénués d'activité d'ARNr-N-gylcosidase ou possédant une activité d'ARNr-N-glycosidase réduite par rapport aux témoins, ainsi que leurs procédés de fabrication et d'utilisation. Les polypeptides et variantes de l'invention sont plus solubles que RTA dans des solutions aqueuses à pH physiologique et à force ionique et conservent également l'intégrité de l'épitope immunologique neutralisant de la RTA de type sauvage. L'invention porte également sur des compositions immunogéniques pouvant être utilisées pour immuniser un sujet contre l'intoxication par le ricin. Des méthodes d'immunisation contre l'intoxication par le ricin, de traitement et de prévention de cette dernière sont également décrites.

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