Recombinant papillomavirus vaccine and method for production and treatment

Abstract

The present invention relates to fusions proteins, comprising a protein or part of a protein that provides T helper epitopes and an antigen from a human-papilloma virus. In particular the invention relates to fusion proteins comprising an E6 or E7 protein from HPV strain 16 or 18 linked to protein D from Haemophilus influenza B. The invention also provides vaccine compositions that are useful in the treatment or prophylaxis of human papilloma induced tumors.

1 . An E6 or E7 protein or E6/E7 fusion protein from HPV linked to an immunological fusion partner.  
     
     
         2 . A protein as claimed in  claim 1  wherein the fusion partner is selected from the group; protein D or a fragment thereof from Heamophilius influenzae B, lipoprotein D or fragment thereof from Heamophilius influenzae B, NS1 or fragment thereof from Influenzae Virus, and LYTA or fragment thereof from  Streptococcus Pneumoniae.    
     
     
         3 . A protein as claimed in  claim 1  or  2  wherein the E6 or E7 proteins are derived from HPV16 or HPV18.  
     
     
         4 . A protein as claimed in  claim 1 ,  2  or  3  wherein the E7 protein is mutated.  
     
     
         5 . A protein as claimed in  claim 1 ,  2  or  3  wherein the E6 protein is mutated.  
     
     
         6 . A protein as claimed in any of  claims 1  to  5  additionally comprising a hisitidine tag of at least 4 hisitidine residues.  
     
     
         7 . A fusion protein comprising a heterologous protein, a hisitidine tag and a C-LYTA tag.  
     
     
         8 . A DNA sequence encoding a protein as claimed herein.  
     
     
         9 . A vaccine containing a protein as claimed in any of  claims 1  to  7  and a pharmaceutically acceptable diluent or excipient.  
     
     
         10 . A vaccine as claimed in  claim 9  additionally comprising an adjuvant.  
     
     
         11 . A vaccine as claimed in  claim 9  or  10  wherein the protein is presented in an oil in water emulsion vehicle.  
     
     
         12 . A vaccine as claimed in  claim 10  or  11  wherein the adjuvant comprises 3D-MPL or QS21 or both.  
     
     
         13 . A vaccine as claimed herein comprising an additional HPV antigen.  
     
     
         14 . A vaccine as claimed herein for use in medicine.  
     
     
         15 . Use of a protein as claimed herein for the manufacture of a vaccine for immunotherapeutically treating a patient suffering from HPV induced tumour lesions (benign or malignant).  
     
     
         16 . Use of a protein as claimed herein for the manufacture of a vaccine to prevent HPV viral infection.  
     
     
         17 . A vector containing a DNA sequence of  claim 8 .  
     
     
         18 . A vector containing a DNA sequence as claimed in  claim 8  and a DNA sequence encoding thioredoxin.  
     
     
         19 . A host transformed with a DNA sequence of  claim 8 .  
     
     
         20 . A host transformed with a vector of  claim 17  or  18 .  
     
     
         21 . A host as claimed in  claim 19  additionally transformed with a DNA sequence encoding thioredoxin.  
     
     
         22 . A process for the production of a protein as claimed herein comprising transforming a host cell with a DNA sequence of  claim 6 , expressing said sequence and isolating the desired product.  
     
     
         23 . A process for the production of a vaccine as claimed herein, comprising admixing a protein as claimed herein with a suitable adjuvant, diluent or other pharmaceutically acceptable excipient.