Peptides derived from Campylobacter jejuni and their use in vaccination

Abstract

Disclosed are polypeptides for Campylobacter jejuni that are useful as immunogenic agents for vaccine use. Also disclosed are nucleic acid fragments encoding the polypeptides as well as compositions, methods and molecular biology tools derived from or related to the proteins.

1 . A polypeptide comprising
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or   b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or   c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or   d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b),   said polypeptide being antigenic in a mammal.   
     
     
         2 . The polypeptide according to  claim 1 , wherein the at least 20 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, and 47 in any one of SEQ ID NOs: 1-30. 
     
     
         3 . The polypeptide according to  claim 1 , wherein the at least 20 contiguous amino acid residues has an N-terminal amino acid residue corresponding to any one of amino acid residues 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, and 258 in any one of SEQ ID NOs: 13-30. 
     
     
         4 . The polypeptide according to  claim 1 , which is fused or conjugated to an immunogenic carrier molecule. 
     
     
         5 . The polypeptide according to  claim 4 , wherein the immunogenic carrier molecule is a polypeptide that induces T-helper lymphocyte responses in a majority of humans. 
     
     
         6 . A pharmaceutical composition comprising a polypeptide and a pharmaceutically acceptable carrier, vehicle or diluent, and which further comprises an immunological adjuvant, said polypeptide comprising:
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or   b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or   c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or   d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b).   
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein the adjuvant is an aluminium based adjuvant. 
     
     
         8 . A method for inducing immunity in an animal by administering at least once an immunogenically effective amount of a polypeptide, said polypeptide comprising:
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or   b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or   c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or   d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b), or   a pharmaceutical composition comprising said polypeptide so as to induce adaptive immunity against  C. jejuni  in the animal.   
     
     
         9 . The method according to  claim 8 , wherein the animal receives between 0.5 and 5,000 μg of the polypeptide according to  claim 1  per administration. 
     
     
         10 . The method according to  claim 8 , wherein the animal is a human being. 
     
     
         11 . The method according to  claim 8 , wherein the immunity is effective in reducing the risk of attracting infection with  C. jejuni  or is effective in treating or ameliorating infection with  C. jejuni.    
     
     
         12 . An isolated nucleic acid fragment, which comprises
 i) a nucleotide sequence encoding a polypeptide, said polypeptide comprising:
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or 
 b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or 
 c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or 
 d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b) or 
   ii) a nucleotide sequence consisting of the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iii) a nucleotide sequence consisting of at least 15 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iv) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in ii),   v) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in iii),   vi) a nucleotide sequence complementary to the nucleotide sequence in i)-v), or   vii) a nucleotide sequence which hybridizes under stringent conditions with the nucleotide sequence in i)-vi).   
     
     
         13 . The nucleic acid fragment according to  claim 12 , which is a DNA fragment or an RNA fragment. 
     
     
         14 . The nucleic acid fragment according to  claim 12 , wherein the sequence identity with the nucleotide sequence in ii) or iii) is at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%. 
     
     
         15 . A vector comprising a nucleic acid fragment, said nucleic acid fragment comprising:
 i) a nucleotide sequence encoding a polypeptide, said polypeptide comprising:
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or 
 b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or 
 c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or 
 d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b) or 
   ii) a nucleotide sequence consisting of the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iii) a nucleotide sequence consisting of at least 15 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iv) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in ii),   v) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in iii),   vi) a nucleotide sequence complementary to the nucleotide sequence in i)-v), or   vii) a nucleotide sequence which hybridizes under stringent conditions with the nucleotide sequence in i)-vi).   
     
     
         16 . The vector according to  claim 15 , which is a cloning vector or an expression vector. 
     
     
         17 . The vector according to  claim 16 , which comprises in operable linkage and in the 5′-3′ direction, an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid fragment defined in  claim 13 - i ), optionally a signal peptide coding sequence, a nucleotide sequence defined in  claim 13 - i ), and optionally a terminator. 
     
     
         18 . The vector according to  claim 13 , which is selected from the group consisting of a virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid. 
     
     
         19 . A method for inducing immunity in an animal by administering at least once an immunogenically effective amount of a nucleic acid, said nucleic acid comprising:
 i) a nucleotide sequence encoding a polypeptide, said polypeptide comprising:
 a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-30, or 
 b) an amino acid sequence consisting of at least 20 contiguous amino acid residues from any one of SEQ ID NOs: 1-30, or 
 c) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of a), or 
 d) an amino acid sequence having a sequence identity of at least 80% with the amino acid sequence of b) or 
   ii) a nucleotide sequence consisting of the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iii) a nucleotide sequence consisting of at least 15 consecutive nucleotides in the amino acid encoding part of any one of SEQ ID NOs: 30-90,   iv) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in ii),   v) a nucleotide sequence having a sequence identity of at least 80% with the nucleotide sequence in iii),   vi) a nucleotide sequence complementary to the nucleotide sequence in i)-v), or   vii) a nucleotide sequence which hybridizes under stringent conditions with the nucleotide sequence in i)-vi) or an expression vector comprising said nucleic acid so as to induce adaptive immunity against  C. jejuni  in the animal.   
     
     
         20 . The method according to  claim 19 , wherein the animal is a human being. 
     
     
         21 . The method according to  claim 19 , wherein the immunity is effective in reducing the risk of attracting infection with  C. jejuni  or is effective in treating or ameliorating infection with  C. jejuni.