Multi-component vaccine comprising at least two antigens from Haemophilus influenzae to protect against disease

Abstract

A multi-component immunogenic composition confers protection on an immunized host against infection caused by Haemophilus influenzae . Such composition comprises at least two different antigens of Haemophilus influenzae , one of which is an adhesin. High molecular weight (HMW) proteins of non-typeable Haemophilus influenzae enhance the immune response in a host to a non-proteolytic analog of Hin47 protein in such immunogenic compositions with one component not impairing the immunogenicity of the other. The Haemophilus vaccine may be combined with DTP component vaccines to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens.

1 - 5 . (canceled)  
     
     
         6 : An immunogenic composition for conferring protection in a host against disease caused by  Haemophilus influenzae , which comprises: 
 an analog of  Haemophilus influenzae  Hin47 protein having a decreased protease activity which is less than about 10% of that of natural Hin47 protein, and    a high molecular weight (HMW) protein of a strain of non-typeable  Haemophilus influenzae.      
     
     
         7 : The composition of  claim 6  wherein said HMW protein is present in said composition in an amount which enhances the immune response in a host to the Hin47 protein.  
     
     
         8 : The composition of  claim 7  wherein said HMW protein is present in the said amount while the individual immunogenicities of the proteins in the composition is are not impaired.  
     
     
         9 : The composition of  claim 6  wherein said analog of Hin47 protein is one in which at least one amino acid of the natural Hin47 protein contributing to protease activity has been deleted or replaced by a different amino acid and which has substantially the saem immunogenic properties as natural Hin47 protein.  
     
     
         10 : The composition of  claim 9  wherein said at least one amino acid is selected from the group consisting of amino acids 91, 121 and 195 to 201 of natural Hin47 protein.  
     
     
         11 : The compostion of  claim 10  wherein Serine-197 is replaced by alanine.  
     
     
         12 : The compostion of  claim 10  wherein Histidine-91 is replaced by alanine, lysine or arginine.  
     
     
         13 : The compostion of  claim 12  wherein Histidine-91 is replaced by alanine.  
     
     
         14 : The composition of  claim 10  wherein Asp-121 is replaced by alanine.  
     
     
         15 : The composition of  claim 8  wherein said HMW protein is an HMW1 or HMW2 protein of a non-typeable strain of  Haemophilus influenzae.    
     
     
         16 : The composition of  claim 15  wherein the HMW 1 and HMW2 proteins are produced recombinantly.  
     
     
         17 : The composition of  claim 15  where said HMW1 and HMW2 proteins are derived from the respective strain of non-typeable  Haemophilus influenzae  and possess respective molecular weights as set forth in the following Table:  
       
         
           
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                   Non-typeable  H. influenzae  Strain 
                 
                 
                 
                 
                 
                 
                 
                 
               
                   Molecular Weight (kDa) 
                   12 
                   JoyC 
                   K21 
                   LCDC2 
                   PMH1 
                   15 
                 
                     
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                   Mature Protein: 
                   HMW1 
                   125 
                   125.9 
                   104.4 
                   114.0 
                   102.4 
                   103.5 
                 
                     
                   HMW2 
                   120 
                   100.9 
                     
                   111.7 
                   103.9 
                   121.9 
                 
                     
                 
                     
                 
             
                
                
                
               
            
             
                
                
               
            
             
                
                
                
                
               
            
           
         
       
     
     
         18 : The composition of  claim 6  further comprising an adjuvant.  
     
     
         19 : The composition of  claim 18  wherein said adjuvant is aluminum hydroxide or aluminum phosphate.  
     
     
         20 : The composition of  claim 6  comprising about 25 to about 100 μg of the Hin47 protein analog, and about 25 to about 100 μg of the HMW protein.  
     
     
         21 : The composition of  claim 6  further comprising at least one additional antigenic component for conferring protection against infection caused by another pathogen.  
     
     
         22 : The composition of  claim 21  wherein said at least one additional antigenic component is selected from the group consisting of diphtheria toxoid, tetanus toxoid, pertussis antigens, non-virulent poliovirus and a conjugate of a tetanus or diphtheria toxoid and a capsular polysaccharide of  Haemophilus influenzae.    
     
     
         23 : The composition of  claim 22  wherein said pertussis antigens are selected from the group consisting of pertussis toxoid, filamentous hemagglutinin, pertactin and agglutinogens.  
     
     
         24 : A method of immunzing a host against disease caused by infection with  Haemophius influenzae , including otitis media, which comprises administering to the host an immunoeffective amount of a composition as claimed in  claim 6.