Vaccine

Abstract

Compositions and methods for the treatment or prevention of Gram-negative bacterial strain infection are provided herein. Methods for the manufacture of said compositions are also provided herein.

We claim: 
     
         1 . An immunogenic composition comprising an antigen which is capable of raising an immune response to an outer membrane protein of at least a first Gram-negative bacterial strain, Wherein said protein is involved in uptake of extracellular zinc. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein the expression of said outer membrane protein is upregulated in response to a low extracellular zinc concentration. 
     
     
         3 . The immunogenic composition of  claim 1 , wherein said first Gram-negative bacterial strain belongs to a bacterial genus or species selected from the group consisting of  Acidovorax; Acinetobacter; Acinetobacter baumannii; Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter johnsonii; Acmetohacter junii; Acinetobacter Iwoffii; Acinetobacter radioresistens; Actinobacillus; Actinobacillus minor; Actinobaciilus pleuropneurnoniae; Aggregatibacter; Aggregatibacter actinornycetemcomitans; Aggregatibacter aphrophilus; Alcanivorax; Alcanivorax borkumensis; Azoarcus; Azotobacter; Azotobacter vinelandii; Bordetella; Bordetella bronchiseptica; Bordetella parapertussis; Bordetella pertussis; Bordetella petrii; Campylobacter; Campylobacter coli; Campylobacter upsaliensis; Comamonas; Comamonas testosteroni; Delftia; Deiftia acidovorans; Diaphorobacter; Haemophilus; Haemophilus influenzae; Haemophilus parasuis; Haemophilus somnus; Mannheimia; Mannheimia haemolytica; Moraxella; Moraxella catarrhalis; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis; Pasteurella; Pasteurella dagmatis; Pasteurella multocida; Proteus Proteus mirabilis; Pseudomonas; Pseudomonas stutzeri ; and  Sphingornonas.    
     
     
         4 . The immunogenic composition of  claim 1 , comprising an antigen comprising a polypeptide having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO 6; SEQ ID NO: 7; SEQ ID NO: 8; SEQ ID NO: 9; SEQ ID NO: 10; SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13; SEQ ID NO: 14; SEQ ID NO: 15; SEQ ID NO: 16; SEQ ID NO: 17; SEQ ID NO: 18; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 21; SEQ ID NO: 22; SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27; SEQ ID NO: 22; SEQ ID NO: 29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32; SEQ II) NO: 33; SEQ ID NO: 34; SEQ ID NO: 35; SEQ ID NO: 36; SEQ ID NO: 37, SEQ. ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40 SEQ ID NO: 41; SEQ ID NO: 42; SEQ NO: 43, SEQ ID NO: 44; SEQ ID NO: 45; SEQ ID NO: 46; SEQ ID NO: 47; SEQ ID NO: 48; SEQ ID NO: 49; SEQ ID NO: 50; SEQ ID NO: 51; SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58; SEQ ID NO: 59; SEQ ID NO: 60; SEQ ID NO: 61; SRI ID NO: 62; SEQ ID NO: 63; SEQ ID NO: 64; SEQ ID NO: 65; SEQ ID NO: 66; SEQ ID NO: 67; SEQ ID NO: 62; SEQ ID NO: 69; SEQ ID NO: 70; and SEQ ID NO: 71. 
     
     
         5 . The immunogenic composition of  claim 1 , comprising an antigen comprising a polypeptide comprising an immunogenic fragment of a sequence selected from the group consisting of SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6; SEQ ID NO: 7; SEQ ID NO: 8; SEQ It) NO: 9; SEQ ID NO: 10; SEQ ID NO: 11; SEQ ID NO: 12; SEQ ID NO: 13; SEQ ID NO: 14; SEQ ID NO: 15; SEQ ID NO: 16; SEQ ID NO: 17; SEQ ID NO: 18; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 21; SEQ ID NO: 22; SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27; SEQ ID NO: 28; SEQ ID NO:29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32; SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 35; SEQ ID NO: 36; SEQ ID NO: 37; SEQ ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40; SEQ ID NO: 41; SEQ ID NO: 42; SEQ ID NO: 43; SEQ ID NO: 44; SEQ ID NO: 45; SEQ ID NO: 46; SEQ ID NO: 47; SEQ ID NO: 48; SEQ ID NO: 49; SEQ ID NO: 50; SEQ ID NO: 51; SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58; SEQ ID NO: 59; SEQ ID NO: 60; SEQ ID NO: 61; SEQ ID NO: 62; SEQ ID NO: 63; SEQ ID NO: 64; SEQ ID NO: 65; SEQ ID NO: 66; SEQ ID NO: 67; SEQ ID NO: 68; SEQ ID NO: 69; SEQ ID NO: 70; and SEQ ID NO: 71, wherein said immunogenic fragment consists of an amino acid sequence having 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 40, 50 or more contiguous amino acids of said selected sequence. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein said immunogenic composition does not comprise a polypeptide having the amino acid sequence of an NMB0964 polypeptide according to PCT/EP2009/052689 or a fragment thereof as disclosed therein, SEQ ID NO: 2 of WO 00/55327 or a fragment thereof as disclosed therein, SEQ ID NO; 606 of WO 99/57280 or a fragment thereof as disclosed therein, or SEQ ID NOs. 2, 4 and 6 of WO 00/11182 or a fragment thereof as disclosed therein. 
     
     
         7 . The immunogenic composition of  claim 1  comprising at least one additional antigen selected from the group consisting of a fHbp polypeptide, a Hsf polypeptide, a Hap polypeptide, a NadA polypeptide and a lipo28 polypeptide, or an immunogenic fragment thereof. 
     
     
         8 . The immunogenic composition of  claim 1 , comprising a bacterial outer membrane vesicle preparation comprising said antigen, wherein expression of said antigen is up-regulated in said outer membrane vesicle preparation. 
     
     
         9 . The immunogenic composition of  claim 1 , further comprising a zinc salt. 
     
     
         10 . An immunogenic composition comprising:
 (a) an antigen, which antigen comprises a polypeptide having at least 95% identity to the amino acid sequence of SEQ ID NO: 50, or   (b) an antigen, which antigen comprises a polypeptide comprising an immunogenic fragment of the sequence of SEQ ID NO: 50, wherein said immunogenic fragment consists of an amino acid sequence having 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50 or more contiguous amino acids of the sequence of SEQ ID NO: 50, wherein said immunogenic fragment is capable of raising an immune response which recognises the amino acid sequence of SEQ ID NO: 50.   
     
     
         11 . The immunogenic composition of  claim 10 , further comprising an antigen comprising a polypeptide having at least 95% to the amino add, sequence of SEQ ID NO: 1, further comprising an antigen comprising a polypeptide comprising an immunogenic fragment of the sequence of SEQ ID NO: 1, wherein said immunogenic fragment consists of an amino acid sequence having 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50 or more contiguous amino acids of the sequence of SEQ ID NO: 1, and wherein said immunogenic fragment is capable of raising, an immune response which recognises the amino acid sequence of SEQ ID NO: 1. 
     
     
         12 . A method for producing an immunogenic composition of  claim 10  comprising: culturing a host cell comprising an expression vector comprising a polynucleotide encoding said antigen under conditions and for a time sufficient for the production of said antigen and recovering the antigen from the culture medium; optionally purifying said antigen by a method selected from the group consisting of ammonium sulphate precipitation, ethanol precipitation, acid extraction, phosphocellulose chromatography, hydrophobic interaction chromatography, hydroxylapatite chromatography and lectin chromatography; and formulating said antigen with a pharmaceutically acceptable carrier or excipient. 
     
     
         13 . A method for producing an immunogenic composition of  claim 10 , comprising culturing at least a first Gram-negative bacterial strain which produces said antigen, wherein said antigen is produced at, a level sufficient to provide for production of outer membrane vesicles that, when administered to a subject, raise a protective response against infection, or disease caused, by at least said first Gram-negative bacterial strain; preparing outer membrane vesicles from the cultured strain; and combining said outer membrane vesicles with a pharmaceutically acceptable carrier or excipient to produce an immunogenic composition suitable for administration to a subject. 
     
     
         14 . A method of preparing an immune globulin for prevention or treatment of Gram-negative bacterial disease, comprising the steps of:
 (a) immunising a recipient with An immunogenic composition comprising an antigen which is capable of raising an immune response to an outer membrane protein of at least a first Gram-negative bacterial strain, wherein said protein is involved in uptake of extracellular zinc; and   (b) isolating immune globulin from the recipient.   
     
     
         15 . The immunogenic preparation obtained from the method of  claim 13 . 
     
     
         16 . A method for the treatment or prevention of Gram-negative bacterial, for instance Neisserial, infection or disease comprising administering a protective dose or an effective amount of the immunogenic composition of  claim 1 .