Genes of an otitis media isolate of nontypeable heamophilus influenzae

Abstract

The invention relates to the polynucleotide sequence of a nontypeable strain of Haemophilus influenza (NTHi) and polypeptides encoded by the polynucleotides and uses thereof. The invention also relates to NTHi genes which are upregulated during or in response to NTHi infection of the middle ear and/or the nasopharynx.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . An isolated polypeptide comprising an amino acid sequence of any one of SEQ ID NO: 616, SEQ ID NO: 618, SEQ ID NO: 620, SEQ ID NO: 622, SEQ ID NO: 624, SEQ ID NO: 626, SEQ ID NO: 628, SEQ ID NO: 628, SEQ ID NO: 630, SEQ ID NO: 632, SEQ ID NO: 634, SEQ ID NO: 636, SEQ ID NO: 638, SEQ ID NO: 640, SEQ ID NO: 642, SEQ ID NO: 644, SEQ ID NO: 646, SEQ ID NO: 648, SEQ ID NO: 650, SEQ ID NO: 652, SEQ ID NO: 654, SEQ ID NO: 656, SEQ ID NO: 658, SEQ ID NO: 660, SEQ ID NO: 662, SEQ ID NO: 664, SEQ ID NO: 666, SEQ ID NO: 668, SEQ ID NO: 670, SEQ ID NO: 672, SEQ ID NO: 674, SEQ ID NO: 687, SEQ ID NO: 689, SEQ ID NO: 691, SEQ ID NO: 693, SEQ ID NO: 695, SEQ ID NO: 697, SEQ ID NO: 699, SEQ ID NO: 701, SEQ ID NO: 703, SEQ ID NO: 705, SEQ ID NO: 707, SEQ ID NO: 709, SEQ ID NO: 711, SEQ ID NO: 713, SEQ ID NO:715, SEQ ID NO: 717, SEQ ID NO: 719, SEQ ID NO: 721, SEQ ID NO:723, SEQ ID NO:725, SEQ ID NO:727, SEQ ID NO:729, SEQ ID NO: 731, SEQ ID NO: 733, SEQ ID NO: 735, SEQ ID NO: 737, SEQ ID NO: 739, SEQ ID NO: 741, SEQ ID NO: 743, SEQ ID NO: 745, SEQ ID NO: 747, SEQ ID NO: 749, SEQ ID NO: 751, SEQ ID NO: 753, SEQ ID NO: 755, SEQ ID NO: 757, SEQ ID NO: 759, SEQ ID NO: 761, 763, SEQ ID NO: 765, SEQ ID NO: 767, SEQ ID NO: 769, SEQ ID NO: 771 or SEQ ID NOS: 2581 to 4414. 
     
     
         4 . A composition comprising a polypeptide of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
         5 . An antibody that specifically binds to a polypeptide of  claim 3  or fragment thereof. 
     
     
         6 . A composition comprising an antibody of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         7 . A method for detecting NTHi bacteria in a biological sample comprising
 (a) contacting an isolated polynucleotide comprising the nucleotide sequence of any one of SEQ ID NOS:577 to 579, SEQ ID NOS: 589 to 614, SEQ ID NOS: 675 to 685, SEQ ID NO: 615, SEQ ID NO: 617, SEQ ID NO: 619, SEQ ID NO: 621, SEQ ID NO: 623, SEQ ID NO: 625, SEQ ID NO: 627, SEQ ID NO: 629, SEQ ID NO: 631, SEQ ID NO: 633, SEQ ID NO: 635, SEQ ID NO: 637, SEQ ID NO: 639, SEQ ID NO: 641, SEQ ID NO: 643, SEQ ID NO: 645, SEQ ID NO: 647, SEQ ID NO: 649, SEQ ID NO: 651, SEQ ID NO: 653, SEQ ID NO: 655, SEQ ID NO: 657, SEQ ID NO: 659, SEQ ID NO: 661, SEQ ID NO: 663, SEQ ID NO: 665, SEQ ID NO: 667, SEQ ID NO: 669, 671, SEQ ID NO: 673, SEQ ID NO: 686, SEQ ID NO: 688, SEQ ID NO: 692, SEQ ID NO: 694, SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 702, SEQ ID NO: 704, SEQ ID NO: 706, SEQ ID NO: 708, SEQ ID NO: 710, SEQ ID NO: 712, SEQ ID NO: 714, SEQ ID NO: 716, SEQ ID NO: 718, SEQ ID NO: 720, SEQ ID NO: 722, SEQ ID NO: 724, SEQ ID NO:726, SEQ ID NO: 728, SEQ ID NO: 730, SEQ ID NO: 732, SEQ ID NO: 734, SEQ ID NO: 736, SEQ ID NO: 738, SEQ ID NO: 740, SEQ ID NO: 742, SEQ ID NO: 744, SEQ ID NO: 746, SEQ ID NO: 748, SEQ ID NO: 750, SEQ ID NO: 752, SEQ ID NO: 754, SEQ ID NO: 756, SEQ ID NO:758, SEQ ID NO:760, SEQ ID NO: 762, SEQ ID NO: 764, SEQ ID NO: 766, SEQ ID NO:768 SEQ ID NO: 770 or SEQ ID NOS: 773 to 2593 or a fragment thereof with a biological sample, and   (b) detecting hybridization of the polynucleotide within the sample.   
     
     
         8 . A method for detecting NTHi bacteria in a biological sample comprising:
 (a) contacting an antibody of  claim 5  with a biological sample, and   (b) detecting binding of the antibody within the sample.   
     
     
         9 . The method of  claim 7  wherein the biological sample is selected from the group consisting of serum, sputum, ear fluid, blood, urine, lymphatic fluid, and cerebrospinal fluid. 
     
     
         10 . A method for eliciting an immune response to NTHi bacteria comprising administering an immunogenically effective dose of a polypeptide of  claim 3  or a fragment thereof to a patient at risk of NTHi bacterial infection. 
     
     
         11 . A vaccine comprising a polypeptide of  claim 3  or a fragment thereof and a pharmaceutically suitable carrier. 
     
     
         12 . The method of  claim 10  wherein the immune response includes one or more of killing NTHi bacteria, slowing replication of NTHi bacteria or blocking binding of NTHi bacteria. 
     
     
         13 . The method of  claim 10  wherein the NTHi infection is in the middle ear. 
     
     
         14 . A method of treating or preventing NTHi bacterial infection comprising administering a molecule that inhibits expression or activity of a polypeptide of  claim 3  to an patient in need. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 14  wherein the molecule administered to the patient in need is an antisense oligonucleotide. 
     
     
         18 . The method of  claim 14  wherein the molecule administered to the patient in need is an antibody. 
     
     
         19 . The method of  claim 14  wherein the molecule administered to the patient in need is a small molecule. 
     
     
         20 . The method of  claim 14  wherein the NTHi infection is in the middle ear. 
     
     
         21 . A vector comprising an isolated polynucleotide comprising the nucleotide sequence of any one of SEQ ID NOS:577 to 579, SEQ ID NOS: 589 to 614, SEQ ID NOS: 675 to 685, SEQ ID NO: 615, SEQ ID NO: 617, SEQ ID NO: 619, SEQ ID NO: 621, SEQ ID NO: 623, SEQ ID NO: 625, SEQ ID NO: 627, SEQ ID NO: 629, SEQ ID NO: 631, SEQ ID NO: 633, SEQ ID NO: 635, SEQ ID NO: 637, SEQ ID NO: 639, SEQ ID NO: 641, SEQ ID NO: 643, SEQ ID NO: 645, SEQ ID NO: 647, SEQ ID NO: 649, SEQ ID NO: 651, SEQ ID NO: 653, SEQ ID NO: 655, SEQ ID NO: 657, SEQ ID NO: 659, SEQ ID NO: 661, SEQ ID NO: 663, SEQ ID NO: 665, SEQ ID NO: 667, SEQ ID NO: 669, 671, SEQ ID NO: 673, SEQ ID NO: 686, SEQ ID NO: 688, SEQ ID NO: 692, SEQ ID NO: 694, SEQ ID NO: 696, SEQ ID NO: 698, SEQ ID NO: 700, SEQ ID NO: 702, SEQ ID NO: 704, SEQ ID NO: 706, SEQ ID NO: 708, SEQ ID NO: 710, SEQ ID NO: 712, SEQ ID NO: 714, SEQ ID NO: 716, SEQ ID NO: 718, SEQ ID NO: 720, SEQ ID NO: 722, SEQ ID NO: 724, SEQ ID NO:726, SEQ ID NO: 728, SEQ ID NO: 730, SEQ ID NO: 732, SEQ ID NO: 734, SEQ ID NO: 736, SEQ ID NO: 738, SEQ ID NO: 740, SEQ ID NO: 742, SEQ ID NO: 744, SEQ ID NO: 746, SEQ ID NO: 748, SEQ ID NO: 750, SEQ ID NO: 752, SEQ ID NO: 754, SEQ ID NO: 756, SEQ ID NO:758, SEQ ID NO:760, SEQ ID NO: 762, SEQ ID NO: 764, SEQ ID NO: 766, SEQ ID NO:768 SEQ ID NO: 770 or SEQ ID NOS: 773 to 2593. 
     
     
         22 . The vector of  claim 21  wherein the vector is operatively linked to an expression control sequence. 
     
     
         23 . An isolated cell comprising the vector of  claim 21 . 
     
     
         24 . An isolated cell comprising the vector of  claim 22 .