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US 2002/0176867 A1Published application
Hybrids of M. tuberculosis antigens
AssigneeStatens Serum Institut
InventorsPeter Andersen, Anja Weinreich Olsen, Rikke Louise Vinther Skjot, Peter Birk Rasmussen
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Abstract
The present invention discloses fusion proteins of the immunodominant antigens ESAT-6 and Ag85B from Mycobacterium tuberculosis or homologues thereof, and a tuberculosis vaccine based on the fusion proteins, which vaccine induces efficient immunological memory.
Claims25
A polypeptide selected from the group consisting of
- (a) a fusion polypeptide which comprises a first amino acid sequence including at least one stretch of amino acids constituting a T-cell epitope derived from the M. tuberculosis protein ESAT-6, and a second amino acid sequence including at least one stretch of amino acids con-stituting a T-cell epitope derived from the M. tuberculosis protein Ag85B, said first and second amino acid sequences optionally being fused via a linker sequence;
- (b) a polypeptide comprising an amino acid sequence analogue having at least 70% sequence identity to the sequence in (a) and at the same time being immunogenic;
- and
- (c) a fusion polypeptide which comprises a first amino acid sequence having at least 70% sequence identity to the first amino acid sequence in (a) and at the same time being immunogenic, and a second amino acid sequence having at least 70% sequence identity to the second amino acid sequence in (a) and at the same time being immunogenic, said first and second amino acid sequences optionally being fused via a linker sequence.
1 more element
A pharmaceutical composition which comprises an immunologically responsive amount of at least one member selected from the group consisting of:
- (a) a fusion polypeptide which comprises a first amino acid sequence including at least one stretch of amino acids constituting a T-cell epitope derived from the M. tuberculosis protein ESAT-6, and a second amino acid sequence including at least one stretch of amino acids con-stituting a T-cell epitope derived from the M. tuberculosis protein Ag85B, said first and second amino acid sequences optionally being fused via a linker sequence;
- (b) a polypeptide comprising an amino acid sequence which has a sequence identity of at least 70% to any one of said polypeptides in (a) and at the same time being immunogenic;
- (c) a fusion polypeptide comprising at least one polypeptide or amino acid sequence according to (a) or (b) and at least one fusion partner;
- (d) a nucleic acid sequence which encodes a polypeptide according to (a), (b) or (c);
- (e) a nucleic acid sequence which is complementary to a sequence according to (d);
- (f) a nucleic acid sequence which has a length of at least 10 nucleotides and which hybridizes under stringent conditions with a nucleic acid sequence according to (d) or (e);
- and
- (g) a non-pathogenic micro-organism which has incorporated (e.g. placed on a plasmid or in the genome) therein a nucleic acid sequence according to (d), (e) or (f) in a manner to permit expression of a polypeptide encoded thereby.
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A method for stimulating an immunogenic response in an animal which comprises administering to said animal an immunologically stimulating amount of at least one member selected from the group consisting of:
- (a) a fusion polypeptide fragment which comprises a first amino acid sequence including at least one stretch of amino acids constituting a T-cell epitope derived from the M. tuberculosis protein ESAT-6, and a second amino acid sequence including at least one stretch of amino acids constituting a T-cell epitope derived from the M. tuberculosis protein Ag85B, said first and second amino acid sequences optionally being fused via a linker sequence;
- (b) a polypeptide comprising an amino acid sequence which has a sequence identity of at least 70% to any one of said polypeptides in (a) and is immunogenic;
- (c) a fusion polypeptide comprising at least one polypeptide or amino acid sequence according to (a) or (b) and at least one fusion partner;
- (d) a nucleic acid sequence which encodes a polypeptide or amino acid sequence according to (a), (b) or (c);
- (e) a nucleic acid sequence which is complementary to a sequence according to (d);
- (f) a nucleic acid sequence which has a length of at least 10 nucleotides and which hybridizes under stringent conditions with a nucleic acid sequence according to (d) or (e);
- and
- (g) a non-pathogenic micro-organism which has incorporated therein (e.g. placed on a plasmid or in the genome) a nucleic acid sequence according to (d), (e) or (f) in a manner to permit expression of a polypeptide encoded thereby.
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Dependencies are inferred from the claim text.