Vaccines

Abstract

The present invention relates to adjuvant compositions which are suitable to be used in vaccines. In particular, the adjuvant compositions of the present invention comprises a saponin and an immunostimulatory oligonucleotide, optionally with a carrier. Also provided by the present invention are vaccines comprising the adjuvants of the present invention and an antigen. Further provided are methods of manufacture of the adjuvants and vaccines of the present invention and their use as medicaments. Methods of treating an individual susceptible to or suffering from a disease by the administration of the vaccines of the present invention are also provided.

1 . An adjuvant composition comprising a saponin and an immunostimulatory oligonucleotide. 
     
     
         2 . An adjuvant composition according to  claim 1  further comprising a carrier. 
     
     
         3 . An adjuvant composition as claimed in  claim 1  or  2 , wherein said saponin is selected from the group comprising Quil A, or purified saponins such as QS21, QS7, QS17; β-escin, or digitonin. 
     
     
         4 . An adjuvant composition as claimed in any one of  claims 1  to  3 , wherein said immunostimulatory oligonucleotide comprises a Purine, Purine, C, G, pyrimidine, pyrimidine sequence. 
     
     
         5 . An adjuvant composition as claimed in  claims 1  to  4 , wherein said immunostimulatory oligonucleotide is selected from the group comprising: 
       
         
           
                 
                 
               
                   (SEQ ID NO:1) 
                     
                 
                 
                 
                 
               
                     
                   TCC ATG ACG TTC CTG ACG TT; 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:2) 
                     
                 
                 
                 
                 
               
                     
                   TCT CCC AGC GTG CGC CAT; 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:3) 
                     
                 
                 
                 
                 
               
                     
                   ACC GAT GAC GTC GCC GGT GAC GGC ACC ACG; 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:4) 
                     
                 
                 
                 
                 
               
                     
                   TCG TCG TTT TGT CGT TTT GTC GTT; 
                     
                 
                     
                     
                 
                 
                 
               
                   (SEQ ID NO:5) 
                     
                 
                 
                 
                 
               
                     
                   TCC ATG ACG TTC CTG ATG CT. 
                     
                 
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
           
         
       
     
     
         6 . An adjuvant composition according to  claim 1  to  4 , wherein the immunostimulatory oligonucleotide contains at least two unmethylated CG repeats being separated at least by 3 nucleotides. 
     
     
         7 . An adjuvant composition according to  claim 6 , wherein the immunostimulatory oligonucleotide contains at least two unmethylated CG repeats being separated by 6 nucleotides. 
     
     
         8 . An adjuvant composition as claimed in any one of  claims 2  to  7 , wherein said carrier is a particulate carrier selected from the group comprising mineral salts, emulsions, polymers, liposomes, ISCOMs. 
     
     
         9 . A vaccine composition comprising an adjuvant composition as claimed in any one of  claims 1  to  8 , further comprising an antigen. 
     
     
         10 . A vaccine composition as claimed in  claim 9 , wherein said antigen is derived from an organism selected from the group comprising: Human Immunodeficiency Virus, Varicella Zoster virus, Herpes Simplex Virus type 1, Herpes Simplex virus type 2, Human cytomegalovirus, Dengue virus, Hepatitis A, B, C or E, Respiratory Syncytial virus, human papilloma virus, Influenza virus, Hib, Meningitis virus,  Salmonella, Neisseria, Borrelia, Chlamydia, Bordetella, Streptococcus, Mycoplasma, Mycobacteria, Haemophilus, Plasmodium  or  Toxoplasma , stanworth decapeptide; or Tumour associated antigens (TAA), MAGE, BAGE, GAGE, MUC-1, Her-2 neu, CEA, PSA, KSA, or PRAME; or a self peptide hormone, GnRH. 
     
     
         11 . A vaccine composition as claimed in  claim 9 , wherein said antigen is derived from the group comprising (a) tumour associated antigens PSMA, PSCA, tyrosinase, survivin, NY-ESO1, prostase, PS108, RAGE, LAGE, HAGE; (b) or the N terminal 39-43 amino acid fragment (A/□□f the amyloid precursor protein; (c) or antigens associated to atherosclerosis. 
     
     
         12 . A vaccine composition as claimed in  claims 9  to  11  wherein the vaccine is administered systemically. 
     
     
         13 . A vaccine composition as claimed in  claims 9  to  11  wherein the vaccine is administered mucosally. 
     
     
         14 . A vaccine composition as claimed in  claim 13  wherein the saponin of the adjuvant composition is haemolytic. 
     
     
         15 . A delivery device pre-filled with the vaccine of  claims 9  to  11 , said device being designed to administer the vaccine systemically. 
     
     
         16 . A method of inducing an immune response in an individual, comprising the systemic administration of a safe and effective amount of the vaccine composition as claimed in  claims 9  to  11 . 
     
     
         17 . A method of treatment of an individual susceptible to or suffering from a disease by the administration to an individual of an effective amount of the vaccine as claimed in any one of  claims 9  to  14 . 
     
     
         18 . A method of treatment as claimed in  claim 17 , wherein the administration of the vaccine is through a systemic route. 
     
     
         19 . A method of treatment of an individual suffering from a disease selected from the group comprising prostate, breast, colorectal, lung, pancreatic, renal, ovarian or melanoma cancers; non-cancer chronic disorders, allergy, Alzheimer, atherosclerosis, comprising the administration of a vaccine as claimed in any one of  claims 9  to  11 . 
     
     
         20 . A method for preventing an individual suffering from contracting a disease selected from the group comprising prostate, breast, colorectal, lung, pancreatic, renal, ovarian or melanoma cancers; non-cancer chronic disorders, allergy, Alzheimer, atherosclerosis, comprising the administration of a vaccine as claimed in any one of  claims 9  to  11 . 
     
     
         21 . A method of treatment as claimed in  claims 19  and  20 , wherein the vaccine is administered via a systemic route. 
     
     
         22 . A vaccine as claimed in  claim 9  or  11  for use as a medicament. 
     
     
         23 . Use of a combination of a saponin and a CpG molecule in the manufacture of a vaccine for the prophylaxis and the treatment of viral, bacterial, parasitic infections, allergy, cancer or other chronic disorders. 
     
     
         24 . Use of combination of a saponin, an immunostimulatory oligonucleotide and a carrier in the manufacture of a vaccine for the prophylaxis and the treatment of viral, bacterial, parasitic infections, allergy, cancer or other chronic disorders. 
     
     
         25 . A method of inducing a systemic antigen specific immune response in a mammal, comprising administering to a mucosal surface of said mammal a composition comprising an antigen and a haemolytic saponin and a CpG molecule. 
     
     
         26 . Method of making an adjuvant composition comprising admixing a saponin with an immunostimulatory oligonucleotide. 
     
     
         27 . Method of making an adjuvant composition comprising admixing a saponin, an immunostimulatory oligonucleotide, and a carrier. 
     
     
         28 . Method of making a vaccine comprising admixing the following (a) a saponin, (b) an immunostimulatory oligonucleotide, and (c) an antigen. 
     
     
         29 . Method of making a vaccine comprising admixing the following (a) a saponin, (b) an immunostimulatory oligonucleotide, (c) a carrier and (d) an antigen.