Immunogens from uropathogenic escherichia coli

Abstract

Disclosed herein are various genes that can be included in immunogenic compositions specific for pathogenic E. coli strains. The genes are from uropathogenic strains but are absent from non-pathogenic strains, and their encoded proteins have cellular locations which render them accessible to the immune system.

We claim: 
     
         1 . A polypeptide composition comprising: an isolated polypeptide comprising (a) an amino acid sequence that is the full-length amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 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, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598 and 599; (b) an amino acid sequence that is at least 80% identical to the full-length amino acid sequence of (a); (c) an amino acid sequence which is a fragment of at least 10 consecutive amino acids from the full-length amino acid sequence of (a); or (d) an amino acid sequence that is at least 80% identical to the full-length amino acid sequence of (a) and includes a fragment of at least 10 consecutive amino acids from the full-length amino acid sequence of (a). 
     
     
         2 . The polypeptide composition of  claim 1 , wherein the isolated polypeptide comprises (i) an amino acid sequence that is the full-length amino acid sequence of (a); (ii) an amino acid sequence that is at least 90% identical to the full-length amino acid sequence of (a); (iii) an amino acid sequence which is a fragment of at least 16 consecutive amino acids from the full-length amino acid sequence of (a); or (d) an amino acid sequence that is at least 90% identical to the full-length amino acid sequence of (a) and includes a fragment of at least 16 consecutive amino acids from the full-length amino acid sequence of (a). 
     
     
         3 . The polypeptide composition of  claim 1 , wherein said fragment comprises at least one B-cell epitope of the full-length amino acid sequence of (a). 
     
     
         4 . The polypeptide composition of  claim 2 , wherein said fragment comprises at least one B-cell epitope of the full-length amino acid sequence of (a). 
     
     
         5 . A pharmaceutical composition comprising the polypeptide composition of any one of  claims 1  to  4 , in admixture with a pharmaceutically acceptable carrier. 
     
     
         6 . A pharmaceutical composition comprising the polypeptide composition of any one of  claims 1  to  4  with two or more polypeptides of any one of  claims 1  to  4 , in admixture with a pharmaceutically acceptable carrier. 
     
     
         7 . An immunogenic composition comprising one or more outer membrane vesicles (OMVs) expressing or overexpressing one or more isolated polypeptides of  claim 1 . 
     
     
         8 . The immunogenic composition of  claim 7 , wherein said fragment comprises at least one B-cell epitope of the full-length amino acid sequence of (a). 
     
     
         9 . A method for raising an immune response in a subject, comprising the step of administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier in admixture with the polypeptide composition of any one of  claims 1  to  4  or the immunogenic composition of  claim 7  or  claim 8 . 
     
     
         10 . The method of  claim 9 , wherein the pharmaceutical composition further comprises an adjuvant. 
     
     
         11 . The method of  claim 9 , wherein the immune response is a protective immune response. 
     
     
         12 . The method of  claim 10 , wherein the immune response is a protective immune response.