US2006251671A1PendingUtilityA1

Haemophilus influenza outer membrane protein and use thereof in vaccination

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Assignee: SMITHKLINE BEECHAM BIOLOGPriority: Feb 15, 2000Filed: Jan 20, 2006Published: Nov 9, 2006
Est. expiryFeb 15, 2020(expired)· nominal 20-yr term from priority
Inventors:Francois-Xavier BerthetPhilippe DenoelJan PoolmanJoelle Thonnard
A61P 37/04A61P 9/00A61P 31/00A61P 27/02A61P 27/16C07K 14/285A61P 11/00A61K 39/00
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Claims

Abstract

This invention relates to recombinant bacterial outer membrane proteins comprising one or more LB1(f) peptides from surface-exposed loop 3 of MOMP P5 of non-typeable H. influenzae . Polynucleotides encoding these recombinant proteins are also covered. The invention also relates to a method of isolating the recombinant proteins and a vaccine composition for use in the treatment of Haemophilus influenzae infection.

Claims

exact text as granted — not AI-modified
1 - 18 . (canceled)  
     
     
         19 . A recombinant bacterial outer membrane protein comprising one or more surface exposed loops, obtainable by a process wherein one or more surface-exposed loops of a native bacterial outer membrane protein from which the recombinant bacterial outer membrane protein is derived have been replaced with one or more modified loops comprising an amino-acid sequence selected from the group consisting of: 
 SEQ. ID NO. 1,    SEQ. ID NO. 2,    SEQ. ID NO. 3, and    SEQ. ID NO. 4    or a sequence which has an identity of at least 75% to said amino-acid sequence and is capable of immunologically mimicking a corresponding antigenic determinant site of the MOMP P5 of non-typeable  Haemophilus influenzae,      with the proviso that the recombinant bacterial outer membrane protein is not identical to a native bacterial outer membrane protein amino-acid sequence.    
     
     
         20 . The recombinant bacterial outer membrane protein of claim  1 , obtainable by a process wherein one or more surface-exposed loops of a native bacterial outer membrane protein from which the recombinant bacterial outer membrane protein is derived have been replaced with one or more modified loops comprising an amino-acid sequence selected from the group consisting of: 
 SEQ. ID NO. 5,    SEQ. ID NO. 6,    SEQ. ID NO. 7, and    SEQ. ID NO. 8    or a sequence which has an identity of at least 75% to said amino-acid sequence and is capable of immunologically mimicking a corresponding antigenic determinant site of the MOMP P5 of non-typeable  Haemophilus influenzae,      with the proviso that the recombinant bacterial outer membrane protein is not identical to a native bacterial outer membrane protein amino-acid sequence.    
     
     
         21 . The recombinant bacterial outer membrane protein of  claim 19 , wherein it is derived from a native outer membrane protein of non-typeable  Haemophilus influenzae  or  Moraxella catarrhalis.    
     
     
         22 . The recombinant bacterial outer membrane protein of  claim 20 , wherein it is derived from a native outer membrane protein of non-typeable  Haemophilus influenzae  or  Moraxella catarrhalis.    
     
     
         23 . The recombinant bacterial outer membrane protein of  claim 19 , wherein it is derived from MOMP P5 of non-typeable  Haemophilus influenzae.    
     
     
         24 . The recombinant bacterial outer membrane protein of  claim 20 , wherein it is derived from MOMP P5 of non-typeable  Haemophilus influenzae.    
     
     
         25 . The modified MOMP P5 protein of  claim 23 , wherein loops 1, 2 and 4 have each been replaced with a modified loop comprising a different LB1(f) peptide selected from the group consisting of: Group 1, 2a, 2b, and 3 peptides, wherein the modified loops comprise an LB1(f) peptide which is from a different Group to the LB1(f) peptide present on loop 3.  
     
     
         26 . The modified MOMP P5 protein of  claim 24 , wherein loops 1, 2 and 4 have each been replaced with a modified loop comprising a different LB1(f) peptide selected from the group consisting of: Group 1, 2a, 2b, and 3 peptides, wherein the modified loops comprise an LB1(f) peptide which is from a different Group to the LB1(f) peptide present on loop 3.  
     
     
         27 . The modified MOMP P5 protein of  claim 23 , wherein loops 1 and 2 have each been replaced with a modified loop comprising a different LB1(f) peptide selected from the group consisting of: Group 1, 2a, 2b and 3 peptides, wherein the modified loops comprise an LB1(f) peptide which is from a different Group to the LB1(f) peptide present on loop 3, and loop 4 has been replaced with a further  H. influenzae  protective epitope.  
     
     
         28 . The modified MOMP P5 protein of  claim 24 , wherein loops 1 and 2 have each been replaced with a modified loop comprising a different LB1(f) peptide selected from the group consisting of: Group 1, 2a, 2b and 3 peptides, wherein the modified loops comprise an LB1(f) peptide which is from a different Group to the LB1(f) peptide present on loop 3, and loop 4 has been replaced with a further  H. influenzae  protective epitope.  
     
     
         29 . The modified MOMP P5 protein of  claim 25 , wherein loop 4 has been replaced with a modified loop comprising a protective epitope from loop 6 of MOMP P2.  
     
     
         30 . The modified MOMP P5 protein of  claim 26 , wherein loop 4 has been replaced with a modified loop comprising a protective epitope from loop 6 of MOMP P2.  
     
     
         31 . The modified MOMP P5 protein of any of claims  23 - 30 , wherein the modified loops comprise an LB1(f) peptide selected from the group consisting of SEQ ID NO:1, 2, 3, 4, 5, 6, 7 and 8.  
     
     
         32 . A vaccine composition comprising an effective amount of the recombinant bacterial outer membrane protein of any of claims  23 - 30  in a pharmaceutically acceptable excipient, and an optional adjuvant.  
     
     
         33 . The use of an immunogenic amount of the recombinant bacterial outer membrane protein of any of claims  23 - 30  in a pharmaceutically acceptable excipient, and an optional adjuvant, to prevent or treat  Haemophilus influenzae  disease.  
     
     
         34 . The use of  claim 33  wherein the  Haemophilus influenzae  disease is otitis media, sinusitis, conjunctivitis, or lower respiratory tract infection.  
     
     
         35 . A method of inducing an immune response in mammal susceptible to  Haemophilus influenzae  infection comprising the administration to the mammal of an effective amount of the vaccine according to  claim 32 .  
     
     
         36 . A method of preventing  Haemophilus influenzae  infection comprising the administration to a mammal an effective amount of a vaccine according to  claim 32 .  
     
     
         37 . A DNA or RNA molecule encoding a recombinant bacterial outer membrane protein as provided in claims  19 - 30 .  
     
     
         38 . An expression vector comprising the DNA or RNA molecule of  claim 37 , wherein said expression vector is capable of expressing said recombinant bacterial outer membrane protein when present in a compatible host cell.  
     
     
         39 . A host cell comprising the expression vector of  claim 37 .  
     
     
         40 . A recombinant host containing the DNA or RNA molecule of  claim 37  within its chromosome, wherein said molecule is in a context suitable for expressing said recombinant bacterial outer membrane protein.  
     
     
         41 . A process for producing a recombinant bacterial outer membrane protein comprising culturing the host cell of  claim 39  and  40  under conditions sufficient for the expression of said protein, and recovering the recombinant bacterial outer membrane protein, or outer membrane vesicles or ghosts comprising said protein.

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