Kennel cough vaccine

Abstract

Improved, low cost vaccines for administration to living subjects such as mammals and birds are provided, which include killed recombinantly modified microorganisms (whole cell recombinant bacterin vaccine), the latter including recombinant DNA encoding at least one protective protein (e.g., an antigenic protein) which has been expressed by the microorganisms prior to killing thereof. The protective protein(s) are operable to prevent or reduce the severity of a disease of the subject. The vaccine preparations of the invention do not require separation of the protective protein(s) from the host recombinant microorganism(s), thereby materially decreasing the complexity and cost of the vaccine formulations. A preferred vaccine against kennel cough includes recombinantly modified microorganisms which express protective antigens containing pertactin and filamentous hemagglutinin protein products.

1 . A kennel cough immunogenic composition for administration to dogs and comprising an effective amount of an immunogenic composition, said composition comprising an effective amount of recombinantly modified and killed bacteria, said bacteria including therein a transformed or transfected recombinant DNA expression vector having DNA encoding at least one protective protein selected from the group consisting of pertactin and filamentous hemagglutinin proteins expressed by the genus  Bordetella  and mixtures thereof, and which has been expressed by the bacteria prior to killing thereof, said effective amount of said bacteria capable of inducing an immune response in said dogs. 
     
     
         2 . The immunogenic composition of  claim 1 , including more than one different bacteria having said transformed or transfected recombinant DNA expression vector. 
     
     
         3 . The immunogenic composition of  claim 1 , said bacteria being  E. coli.    
     
     
         4 . The immunogenic composition of  claim 1 , said expression vector being a plasmid vector within said bacteria. 
     
     
         5 . The immunogenic composition of  claim 1 , including a pharmaceutically acceptable carrier. 
     
     
         6 . The immunogenic composition of  claim 1 , including an adjuvant. 
     
     
         7 . The immunogenic composition of  claim 1 , said immunogenic composition including bacteria which express fusion proteins including protein fragments selected from the group consisting of SEQ IDS Nos. 6, 7, and 9, and mixtures thereof. 
     
     
         8 . A method of inducing an immune response in dogs comprising the step of administering to a dog an immunogenic composition, said composition comprising an effective amount of recombinantly modified and killed bacteria, said bacteria including therein a transformed or transfected recombinant DNA expression vector having DNA encoding at least one protective protein selected from the group consisting of pertactin and filamentous hemagglutinin proteins expressed by the genus  Bordetella  and mixtures thereof, and which has been expressed by the bacteria prior to killing thereof, said effective amount of said bacteria capable of inducing an immune response in said dogs. 
     
     
         9 . The method of  claim 8 , said bacteria being  E. coli.    
     
     
         10 . The method of  claim 9 , said immunogenic composition including  E. coli  which expresses fusion proteins selected from the group consisting of SEQ IDS Nos. 6, 7, and 9, and mixtures thereof. 
     
     
         11 . The method of  claim 8 , said protective protein being a fusion protein. 
     
     
         12 . The method of  claim 8 , said immunogenic composition including a pharmaceutically acceptable carrier. 
     
     
         13 . The method of  claim 8 , said immunogenic composition including an adjuvant. 
     
     
         14 . A method of preparing an immunogenic composition for administration to a living subject comprising the steps of:
 providing microorganisms including therein recombinant DNA encoding at least one protective protein operable to prevent or reduce the severity of said disease of said subject;   causing said microorganisms to express said at least one protective protein; and   killing said microorganisms after said protein expression.   
     
     
         15 . The method of  claim 14 , including the step of providing more than one different microorganism having different recombinant DNA therein, respectively. 
     
     
         16 . The method of  claim 14 , said microorganisms selected from the group consisting of bacteria and yeast. 
     
     
         17 . The method of  claim 16 , said microorganisms being bacteria. 
     
     
         18 . The method of  claim 17 , said bacteria being  E. coli.    
     
     
         19 . The method of  claim 14 , said recombinant DNA being present as a part of a recombinant DNA element within said microorganisms. 
     
     
         20 . The method of  claim 14 , said at least one protective protein being a fusion protein. 
     
     
         21 . The method of  claim 14 , said protective protein being an antigen capable of inducing an immune response in said subject when the antigen is present in an effective amount. 
     
     
         22 . The method of  claim 14 , said subject selected from the group consisting of mammals and birds. 
     
     
         23 . The method of  claim 22 , said subject selected from the group consisting of humans, livestock and domestic pets. 
     
     
         24 . The method of  claim 14 , including the step of adding a pharmaceutically acceptable carrier to said microorganisms. 
     
     
         25 . The method of  claim 14 , including the step of adding an adjuvant to said microorganisms. 
     
     
         26 . The method of  claim 14 , said immunogenic composition being a kennel cough immunogenic composition. 
     
     
         27 . The method of  claim 26 , said immunogenic composition including microorganisms which express protective proteins selected from the group consisting of pertactin and filamentous hemagglutinin proteins, fragments of such proteins, and mixtures thereof. 
     
     
         28 . The method of  claim 27 , said immunogenic composition including microorganisms which express fusion proteins including protein fragments selected from the group consisting of SEQ IDS Nos. 5, 6, 7, 8 and 9, and mixtures thereof.