Clostridium difficile toxin-based vaccine

摘要

An immunogenic composition comprising a combination of Clostridium difficile antigens, said combination comprising a) a ToxB-GT antigen consisting of an amino acid sequence: (a) having 80% or more identity with respect to SEQ ID NO: 18 or SEQ ID NO: 60; and / or b) that it is a fragment of at least 50 consecutive amino acids of SEQ ID NO: 18 or SEQ ID NO: 60 or of a polypeptide that has 80% or more identity with respect to SEQ ID NO: 18 or SEQ ID NO: 60 and comprising an epitope of SEQ ID NO: 18 or SEQ ID NO: 60; wherein the ToxB-GT antigen is detoxified and comprises one or more amino acid substitutions at amino acid positions 17, 102, 139, 269, 270, 273, 284, 286, 288, 384, 449, 444, 445, 448 , 449, 450, 451, 452, 455, 461, 463, 472, 515, 518 and 520, in relation to the wild-type 10 ToxB-GT antigen sequence of SEQ ID NO: 18 and in which the two substitutions amino acids are not found at positions corresponding to amino acids 102 and 278 of SEQ ID NO: 18 or positions 102 and 288 of SEQ ID NO: 18; and b) a ToxA-P5-6 antigen consisting essentially of an amino acid sequence having 80% or 15% more identity than SEQ ID NO: 11.