Polyanionic polymer adjuvants for haemophilus influenzae b saccharide vaccines

Abstract

The present invention relates to immunogenic compositions comprising capsular polysaccharide or oligosaccharide of H. influenzae B (PRP) and methods of making such compositions.

We claim: 
     
         1 . An immunogenic composition comprising a capsular polysaccharide or oligosaccharide of  Haemophilus influenzae  B (PRP), and a polyanionic polymer which is an oligo- or poly-peptide consisting of, on average, 8-117 residues and comprising anionic constitutional repeating units obtained from a group consisting of: L-aspartic acid, D-aspartic acid, L-glutamic acid, D-glutamic acid, and salts of the foregoing. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein PRP is conjugated to a carrier protein which is a source of T-helper cell epitopes. 
     
     
         3 . The immunogenic composition of  claim 2 , wherein the carrier protein is selected from the group consisting of: tetanus toxoid, diphtheria toxoid, CRM197, and protein D. 
     
     
         4 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is an oligo- or poly-peptide which has a monomer content of 100% L-aspartic acid and/or L-glutamic acid. 
     
     
         5 . The immunogenic composition of  claim 1 , wherein the oligo- or polypeptide consists of, on average, 15-18 residues. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is polyanionic heteropolymer. 
     
     
         7 . The immunogenic composition of  claim 6 , wherein the polyanionic heteropolymer consists of two distinct anionic constitutional repeating units. 
     
     
         8 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is a polyanionic homopolymer. 
     
     
         9 . The immunogenic composition of  claim 1 , wherein the polyanionic polymer is poly-L-glutamic acid (PLG). 
     
     
         10 . The immunogenic composition of  claim 1 , wherein the immunogenic composition comprises one or more further antigens. 
     
     
         11 . The immunogenic composition of  claim 10 , wherein the one or more further antigens comprise one or more meningococcal capsular oligosaccharide or polysaccharide-carrier protein conjugates selected from a group consisting of: MenC, MenY, MenA and MenW, preferably MenC and/or MenY. 
     
     
         12 . The immunogenic composition of  claim 10 , wherein the one or more further antigens comprise one or more pneumococcal capsular oligosaccharide or polysaccharide-carrier protein conjugates. 
     
     
         13 . The immunogenic composition of  claim 11 , wherein the carrier protein is selected from the group consisting of: tetanus toxoid, diphtheria toxoid, CRM197, and protein D. 
     
     
         14 . The immunogenic composition of  claim 10 , wherein the one or more further antigens comprise tetanus toxoid, diphtheria toxoid, and inactivated whole-cell  B. pertussis  or one or more acellular  B. pertussis  antigens. 
     
     
         15 . The immunogenic composition of  claim 10 , wherein the one or more further antigens comprise one or more acellular  B. pertussis  antigens selected from the group consisting of: pertussis toxiod, FHA, pertactin, agglutinogen 2 and agglutinogen 3. 
     
     
         16 . The immunogenic composition of  claim 10 , wherein the one or more further antigens comprise either or both of Inactivated Polio Vaccine (IPV) and Hepatitis B surface antigen, wherein Hepatitis B surface antigen is preferably adsorbed onto aluminium phosphate. 
     
     
         17 . The immunogenic composition of  claim 1 , which is lyophilised and further comprises a stabilizing excipient selected from the group consisting of: glucose, maltulose, iso-maltulose, lactulose, sucrose, sorbitol, maltose, lactose, iso-maltose, maltitol, lactitol, palatinit, trehalose, raffinose, stachyose, and melezitose; preferably sucrose. 
     
     
         18 . A vaccine comprising the immunogenic composition of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         19 . A method of preventing or treating  H. influenzae  B disease comprising the step of administering a pharmaceutically effective amount of the vaccine of  claim 18  to a patient in need thereof. 
     
     
         20 . The immunogenic composition of  claim 12 , wherein the carrier protein is selected from the group consisting of: tetanus toxoid, diphtheria toxoid, CRM197, and protein D.