Anti-bacterial Vaccine Compositions

Abstract

Gram negative bacterial virulence genes are identified, thereby allowing the identification of novel anti-bacterial agents that target these virulence genes and their products, and the provision of novel gram negative bacterial mutants useful in vaccines.

1 - 76 . (canceled) 
     
     
         77 . An attenuated Pasteurellaceae bacterium selected from the group consisting of  Pasteurella  ( Mannheimia )  haemolytica, Pasteurella multocida , and  Actinobacillus pleuropneumoniae  comprising a mutation in a polynucleotide sequence that encodes a fhaC polypeptide comprising an amino acid sequence at least 70% identical to the fhaC amino acid sequence of SEQ ID NO: 20, wherein the mutation results in decreased virulence and attenuation of the bacterium. 
     
     
         78 . The bacterium of  claim 77 , wherein the mutation results in deletion of all or part of the polynucleotide sequence that encodes the fhaC polypeptide. 
     
     
         79 . The bacterium of  claim 77 , wherein the mutation results in an insertion in the polynucleotide sequence that encodes the fhaC polypeptide. 
     
     
         80 . The bacterium of  claim 77  that is a  Pasteurella multocida  bacteria. 
     
     
         81 . An immunogenic composition comprising a bacterium according to  claim 77 . 
     
     
         82 . A vaccine composition comprising the immunogenic composition according to  claim 81  and a pharmaceutically acceptable carrier. 
     
     
         83 . The vaccine composition according to  claim 82 , further comprising an adjuvant. 
     
     
         84 . An attenuated Pasteurellaceae bacterium selected from the group consisting of  Pasteurella  ( Mannheimia )  haemolytica, Pasteurella multocida , and  Actinobacillus pleuropneumoniae  comprising a mutation in a polynucleotide sequence that encodes a fhaC polypeptide, wherein the polynucleotide sequence hybridizes to the complement of a polynucleotide sequence set forth in SEQ ID NO: 19 under stringent conditions, such conditions comprising a final wash in buffer comprising 2×SSC/0.1% SDS, at 35° C. to 45° C. 
     
     
         85 . The bacterium of  claim 84 , wherein the mutation is in the polynucleotide sequence set forth in SEQ ID NO: 19. 
     
     
         86 . An immunogenic composition comprising the bacterium according to  claim 84  or  claim 85 . 
     
     
         87 . A vaccine composition comprising the immunogenic composition according to  claim 87  and a pharmaceutically acceptable carrier. 
     
     
         88 . The vaccine composition of  claim 87 , further comprising an adjuvant. 
     
     
         89 . An attenuated  Pasteurella multocida  bacterium comprising a mutation in a polynucleotide sequence set forth in SEQ ID NO: 19 that encodes a fhaC polypeptide, wherein the mutation results in decreased virulence and attenuation of the bacterium. 
     
     
         90 . The bacterium of  claim 89 , wherein the mutation results in deletion of all or part of the polynucleotide sequence that encodes the fhaC polypeptide. 
     
     
         91 . The bacterium of  claim 89 , wherein the mutation results in an insertion in the polynucleotide sequence that encodes the fhaC polypeptide. 
     
     
         92 . An immunogenic composition comprising a bacterium according to  claim 89 . 
     
     
         93 . A vaccine composition comprising the immunogenic composition according to  claim 92  and a pharmaceutically acceptable carrier.