Multivalent vaccine composition

Abstract

A multi-valent vaccine composition is described comprising a conjugate of the capsular polysaccharide of H. influenzae b not adsorbed onto an aluminium adjuvant salt, and two or more further bacterial polysaccharides. A multi-valent vaccine composition is also described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, Hepatitis B surface antigen, a conjugate of the capsular polysaccharide of H. influenzae b, and a conjugate of a capsular polysaccharide of N. meningitidis type A or C (or both). Furthermore, a multi-valent vaccine composition is described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, and a low dose of a conjugate of the capsular polysaccharide of H. influenzae b.

We claim:  
     
         1 . A multi-valent immunogenic composition comprising a conjugate of a carrier protein and the capsular polysaccharide of  H. influenzae  type B, wherein said composition additionally comprises 2 or more further bacterial polysaccharides capable of conferring protection to a host against infection by the bacteria from which they are derived, and wherein the  H. influenzae  type B capsular polysaccharide conjugate is not adsorbed onto an aluminium adjuvant salt.  
     
     
         2 . The multi-valent immunogenic composition of  claim 1 , which comprises more than 7 further bacterial polysaccharides.  
     
     
         3 . The multi-valent immunogenic composition of  claim 2 , wherein the further bacterial polysaccharides are pneumococcal capsular polysaccharides.  
     
     
         4 . The multi-valent immunogenic composition of claims  1 - 3 , wherein none of the polysaccharides in the composition are adsorbed onto an aluminium adjuvant salt.  
     
     
         5 . The multi-valent immunogenic composition of claims  1 - 4 , wherein the further bacterial polysaccharides are selected from a group consisting of:  N. meningitidis  serogroup A capsular polysaccharide,  N. meningitidis  serogroup C capsular polysaccharide,  N. meningitidis  serogroup Y capsular polysaccharide,  N. meningitidis  serogroup W capsular polysaccharide,  Streptococcus pneumoniae  serotype 1 capsular polysaccharide,  S. pneumoniae  serotype 2 capsular polysaccharide,  S. pneumoniae  serotype 3 capsular polysaccharide,  S. pneumoniae  serotype 4 capsular polysaccharide,  S. pneumoniae  serotype 5 capsular polysaccharide,  S. pneumoniae  serotype 6A capsular polysaccharide,  S. pneumoniae  serotype 6B capsular polysaccharide,  S. pneumoniae  serotype 7F capsular polysaccharide,  S. pneumoniae  serotype 8 capsular polysaccharide,  S. pneumoniae  serotype 9N capsular polysaccharide,  S. pneumoniae  serotype 9V capsular polysaccharide,  S. pneumoniae  serotype 10A capsular polysaccharide,  S. pneumoniae  serotype 11A capsular polysaccharide,  S. pneumoniae  serotype 12F capsular polysaccharide,  S. pneumoniae  serotype 14 capsular polysaccharide,  S. pneumoniae  serotype 15B capsular polysaccharide,  S. pneumoniae  serotype 17F capsular polysaccharide,  S. pneumoniae  serotype 18C capsular polysaccharide,  S. pneumoniae  serotype 19A capsular polysaccharide,  S. pneumoniae  serotype 19F capsular polysaccharide,  S. pneumoniae  serotype 20 capsular polysaccharide,  S. pneumoniae  serotype 22F capsular polysaccharide,  S. pneumoniae  serotype 23F capsular polysaccharide,  S. pneumoniae  serotype 33F capsular polysaccharide, Group B Streptococcus group I capsular polysaccharide, Group B Streptococcus group II capsular polysaccharide, Group B Streptococcus group III capsular polysaccharide, Group B Streptococcus group IV capsular polysaccharide, Group B Streptococcus group V capsular polysaccharide,  Staphylococcus aureus  type 5 capsular polysaccharide,  Staphylococcus aureus  type 8 capsular polysaccharide, Vi polysaccharide from  Salmonella typhi, N. meningitides  LPS,  M. catarrhalis  LPS, and  H. influenzae  LPS.  
     
     
         6 . The multi-valent immunogenic composition of claims  1 - 5 , wherein the further bacterial polysaccharides are conjugated to a carrier protein.  
     
     
         7 . The multi-valent immunogenic composition of claims  1 - 6 , wherein the carrier protein(s) used is selected from the group comprising: tetanus toxoid, diphtheria toxoid, CRM197, recombinant diphtheria toxin, OMPC from  N. meningitidis , pneumolysin from  S. pneumoniae  and protein D from  H. influenzae.    
     
     
         8 . The multi-valent immunogenic composition of  claim 6  or  7 , wherein the capsular polysaccharide of  H. influenzae  type B and the further polysaccharides are not conjugated to the same carrier.  
     
     
         9 . The multi-valent immunogenic composition of  claim 8 , wherein the capsular polysaccharide of  H. influenzae  type B and the further polysaccharides are not all conjugated to CRM197.  
     
     
         10 . The use of the multi-valent immunogenic composition of claims  1 - 9  in the manufacture of a medicament for the treatment or prevention of diseases caused by infection by  Haemophilus influenzae.    
     
     
         11 . A method of immunising a human host against disease caused by  Haemophilus influenzae , which method comprises administering to the host an immunoprotective dose of the multi-valent immunogenic composition of claims  1 - 9 .  
     
     
         12 . A multi-valent immunogenic composition for conferring protection in a host against disease caused by  Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus,  Haemophilus influenzae  and  N. meningitidis  comprising: 
 a) either killed whole-cell  Bordetella pertussis , or two or more acellular pertussis components,    b) tetanus toxoid,    c) diphtheria toxoid,    d) Hepatitis B surface antigen,    e) a conjugate of a carrier protein and the capsular polysaccharide of  H. influenzae  type B, and    f) one or more conjugates of a carrier protein and a capsular polysaccharide of a bacterium selected from the group  N. meningitidis  type A and  N. meningitidis  type C.    
     
     
         13 . The immunogenic composition of  claim 12  further comprising one or more conjugates of a carrier protein and a capsular polysaccharide of a bacterium selected from the group  N. meningitidis  type Y and  N. meningitidis  type W.  
     
     
         14 . The immunogenic composition of  claim 12  or  13  further comprising killed, attenuated Hepatitis A virus.  
     
     
         15 . The immunogenic composition of claims  12 - 14  further comprising inactivated polio virus.  
     
     
         16 . The immunogenic composition of claims  12 - 15  wherein the carrier protein(s) used is selected from the group comprising: tetanus toxoid, diphtheria toxoid, CRM197, recombinant diphtheria toxin, OMPC from  N. meningitidis , and protein D from  H influenzae.    
     
     
         17 . The immunogenic composition of claims  12 - 16  formulated as a vaccine for in vivo administration to the host wherein the individual components of the composition are formulated such that the immunogenicity of individual components is not impaired by other individual components of the composition.  
     
     
         18 . The immunogenic composition of claims  12 - 16  formulated as a vaccine for in vivo administration to the host, which confers an antibody titre superior to the criterion for seroprotection for each antigenic component for an acceptable percentage of human subjects.  
     
     
         19 . The immunogenic composition of claims  12 - 18  further comprising an adjuvant.  
     
     
         20 . The immunogenic composition of  claim 19  wherein the adjuvant is aluminium salts.  
     
     
         21 . The multi-valent immunogenic composition of claims  1 - 9  and  12 - 20  for use in a medicament.  
     
     
         22 . The use of the immunogenic composition of claims  12 - 20  in the manufacture of a medicament for the treatment or prevention of diseases caused by infection by  Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus,  Haemophilus influenzae  and  N. meningitidis.    
     
     
         23 . A method of immunising a human host against disease caused by  Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus,  Haemophilus influenzae  and  N. meningitidis , which method comprises administering to the host an immunoprotective dose of the immunogenic composition of claims  12 - 20 .  
     
     
         24 . A process for making the multi-valent immunogenic composition of claims  1 - 9  and  12 - 20  comprising the step of mixing together the individual components.  
     
     
         25 . A multi-valent immunogenic composition comprising killed whole-cell  Bordetella pertussis , tetanus toxoid, diphtheria toxoid, and a conjugate of a carrier protein and the capsular polysaccharide of  H. influenzae  type B, wherein the amount of conjugate per 0.5 mL dose of bulk vaccine is 1-8 μg, and the immunogenicity of the conjugate is equivalent or improved over such compositions comprising larger amounts of conjugate.  
     
     
         26 . The immunogenic composition of  claim 25  wherein the carrier protein used is selected from the group comprising: tetanus toxoid, diphtheria toxoid, CRM197, OMPC from  N. meningitidis , and protein D from  H. influenzae.    
     
     
         27 . The immunogenic composition of  claim 25  or  26  wherein the amount of conjugate per 0.5 mL dose of bulk vaccine is 3-6 μg.  
     
     
         28 . The immunogenic composition of  claim 25  or  26  wherein the amount of conjugate per 0.5 mL dose of bulk vaccine is 5 μg.  
     
     
         29 . The immunogenic composition of claims  25 - 28 , wherein the conjugate of a carrier protein and the capsular polysaccharide of  H. influenzae  type B is not adsorbed onto an aluminium adjuvant salt.