Proteins and nucleic acids useful in vaccines targeting Staphylococcus aureus

Abstract

Disclosed are novel immunogenic proteins derived from Staphylococcus aureus , as well as methods for their use in conferring protective immunity against S. aureus infections. Also disclosed are nucleic acids encoding the proteins and methods of use of these nucleic acids.

1 . A polypeptide comprising
 a) an amino acid sequence consisting of SEQ ID NO: 14, or   b) an amino acid sequence consisting of at least 35 contiguous amino acid residues from SEQ ID NO: 14, or   c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of a) or b),   
       said polypeptide being antigenic in a mammal. 
     
     
         2 . The polypeptide according to  claim 1 , wherein the sequence identity defined in c) or d) is at least 65%, such as at least 70%, at least 75%, at least 80%, 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%. 
     
     
         3 . The polypeptide according to  claim 1 , wherein the at least 35 contiguous amino acid residues of option b) 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, 47, 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, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, and 362 in SEQ ID NO: 14, 
       wherein the N-terminal first residue will not be higher numbered than 397-L, where L is the number of amino acids defined for option b. 
     
     
         4 . The polypeptide according to  claim 1 , which is fused or conjugated to an immunogenic carrier molecule. 
     
     
         5 . The polypeptide according to 4, wherein the immunogenic carrier molecule is a polypeptide that induces T-helper lymphocyte responses in a majority of humans, such as an immunogenic carrier protein selected from the group consisting of keyhole limpet hemocyanin or a fragment thereof, tetanus toxoid or a fragment thereof, diphtheria toxoid or a fragment thereof. 
     
     
         6 . The polypeptide according to  claim 1 , which is capable of inducing an adaptive protective immune response against infection with multi-resistant  S. aureus  in a mammal, in particular in a human being. 
     
     
         7 . The polypeptide according to  claim 6 , which induces a humeral and/or a cellular immune response. 
     
     
         8 . An isolated nucleic acid fragment, which comprises a nucleotide sequence encoding a polypeptide according to  claim 1 . 
     
     
         9 . The nucleic acid fragment according to  claim 8 , which is a DNA fragment or an RNA fragment. 
     
     
         10 . The nucleic acid fragment according to  claim 9 , which comprises SEQ ID NO: 33 or 52, or a fragment thereof, which encodes a polypeptide. 
     
     
         11 . A vector comprising the nucleic acid according to  claim 8 , such as a cloning vector or an expression vector. 
     
     
         12 . The vector according to  claim 11 , 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 8 , optionally a signal peptide coding sequence, a nucleotide sequence defined in  claim 8 , and optionally a terminator. 
     
     
         13 . The vector according to  claim 12 , which is incapable of being integrated into the genome of a mammalian host cell. 
     
     
         14 . The vector according to  claim 11 , which is selected from the group consisting of a virus, such as a attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid. 
     
     
         15 . A cell which is transformed so as to carry the vector according to  claim 11 . 
     
     
         16 . The cell according to  claim 15 , which is capable of expressing the nucleic acid fragment defined in  claim 8 . 
     
     
         17 . The cell according to  claim 15 , which is a bacterial cell selected from the group consisting of  Escherichia  (such as  E. coli .),  Bacillus  [e.g.  Bacillus subtilis ],  Salmonella , and  Mycobacterium  [preferably non-pathogenic, e.g.  M. bovis  BCG]. 
     
     
         18 . A pharmaceutical composition comprising the polypeptide according to  claim 1 , the nucleic acid fragment according to  claim 8 , the vector according to  claim 11 , or the cell according to  claim 15 , and a pharmaceutically acceptable carrier, vehicle or diluent. 
     
     
         19 . The pharmaceutical composition according to  claim 18 , which further comprises an immunological adjuvant. 
     
     
         20 . The pharmaceutical composition according to  claim 19 , wherein the adjuvant is an aluminium based adjuvant. 
     
     
         21 . A method for inducing immunity in an animal by administering at least once an immunogenically effective amount of the polypeptide according to any  claim 1 , the nucleic acid fragment according to  claim 8 , the vector according to  claim 11 , or the cell according to  claim 15 , or a pharmaceutical composition according to  claim 18  so as to induce adaptive immunity against  S. aureus  in the animal. 
     
     
         22 . The method according to  claim 21 , wherein, when the polypeptide according to  claim 1  or a composition comprising said polypeptide is administered, the animal receives between 0.5 and 5,000 μg of the polypeptide according to  claim 1  per administration. 
     
     
         22 . The method according to  claim 21 , wherein the animal receives a priming administration and one or more booster administrations. 
     
     
         23 . The method according to  claim 21 , wherein the animal is a human being. 
     
     
         24 . The method according to  claim 21 , wherein the administration is for the purpose of inducing protective immunity against  S. aureus.    
     
     
         25 . The method according to  claim 24 , wherein the protective immunity is effective in reducing the risk of attracting infection with  S. aureus  or is effective in treating or ameliorating infection with  S. aureus.