Immunogenic detoxified mutants of cholera toxin and of the...

Details Immunogenic detoxified mutants of cholera toxin and of the... Immunogenic detoxified mutants of cholera toxin and of the...

C - Chemistry, Metallurgy

12

N

C12N 15/31 (2006.01) A61K 39/106 (2006.01) A61K 39/108 (2006.01) C07K 14/245 (2006.01) C07K 14/28 (2006.01) C12N 15/10 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2127091

An immunogenic detoxified protein comprising the amino acid sequence of subunit A of cholera toxin (CT-A) or subunit A of an Escherichia coli heat labile toxin (LT-A) or a fragment thereof wherein one or more amino acids at, or in positions corresponding to Val-53, Ser-63, Val-97, Tyr-104 or Pro-106 are replaced with another amino acid or deleted. Examples of specific replacements include Val-53-Asp; Val-53-Glu, Val-53-Tyr, Ser-63-Lys; Val-97-Lys, Val-97-Tyr, Tyr-104-Lys, Tyr-104-Asp, Tyr-104-Ser, Pro-106-Ser. The immunogenic detoxified protein is useful as vaccine for Vibrio cholerae or an enterotoxigenic strain of Escherichia coli and is produced by recombinant DNA means by site-directed mutagenesis.

Protéine immunogéne détoxiquée comprenant la séquence d'aminoacide de la sous-unité A de la toxine du choléra (CT-A) ou de la sous-unité A d'une toxine thermolabile (LT-A) de l'Escherichia coli, ou un fragment de ces sous-unités, un ou plusieurs aminoacides dans les positions correspondant à Val-53, Ser-63, Val-97, Tyr-104 ou Pro-106 étant substitués par un autre aminoacide ou perdus. Des exemples de substitutions spécifiques comprennent Val-53-Asp, Val-53-Glu, Val-53-Tyr, Ser-63-Lys, Val-97-Lys, Val-97-Tyr, Tyr-104-Lys, Tyr-104-Asp, Tyr-104-Ser, Pro-106-Ser. Cette protéine immunogénique détoxiquée peut être utilisée comme vaccin contre le Vibrio cholerae ou une souche entérotoxigénique d'Escherichia coli, et est produite par recombinaison d'ADN par mutagenèse dirigée.

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