Immune modulation

Abstract

The present invention relates to a poxvirus vector comprising a nucleic acid sequence encoding a fusion protein comprising: (i) a peanut allergen selected from list consisting of at least two peanut allergens from ara h 1, ara h 2, ara h 3, ara h 4, ara h 5, ara h 6, ara h 7, ara h 8, ara h 9, ara h 8, ara h 9, ara h 10 and ara h 11 or a derivative or part thereof having at least 70% sequence identity thereto, and (ii) a proteasome degradation tag to enhance intracellular degradation of the fusion protein.

1 . A poxvirus vector comprising a nucleic acid sequence encoding a fusion protein comprising:
 (i) at least two peanut allergens selected from the group consisting of ara h 1, ara h 2, ara h 3, ara h 4, ara 5, ara h 6, ara h 7, ara h 8, ara h 9, ara h 10 and ara h 11, and a derivative or part thereof having at least 70% sequence identity thereto, and   (ii) a proteasome degradation tag to enhance intracellular degradation of the fusion protein.   
     
     
         2 . The poxvirus vector of  claim 1 , wherein the nucleic acid sequence encodes a fusion protein comprising:
 (i) at least two peanut allergens selected from list consisting of ara h 1, ara h 2, ara h 3, ara h 4, ara h 5, ara h 6 and ara h 7, and a derivative or part thereof having at least 70% sequence identity thereto, and   (ii) a proteasome degradation tag to enhance intracellular degradation of the fusion protein.   
     
     
         3 . The poxvirus vector of  claim 1 , wherein the nucleic acid sequence encodes a fusion protein comprising:
 (i) at least three peanut allergens selected from the group consisting of ara h 1, ara h 2, ara h 3, ara h 4, ara h 5, ara h 6, ara h 7, ara h 8, ara h 9, ara h 10 and ara h 11, and a derivative or part thereof having at least 70% sequence identity thereto, and   (ii) a proteasome degradation tag to enhance intracellular degradation of the fusion protein.   
     
     
         4 . The poxvirus vector of  claim 3 , wherein the nucleic acid sequence encodes a fusion protein comprising:
 (i) at least three peanut allergens selected from the group consisting of ara h 1, ara h 2, ara h 3, ara h 4, ara h 5, ara h 6 and ara h 7, and a derivative or part thereof having at least 70% sequence identity thereto, and   (ii) a proteasome degradation tag to enhance intracellular degradation of the fusion protein.   
     
     
         5 . The poxvirus vector of  claim 1 , wherein the vector comprises a promoter and single start codon to facilitate expression of the intact fusion protein. 
     
     
         6 . The poxvirus vector of  claim 1 , wherein the proteasome degradation tag comprises a ubiquitin monomer. 
     
     
         7 . The poxvirus vector of  claim 1 , wherein the nucleic acid sequence encodes a fusion protein comprising four peanut allergens which are ara h 1, ara h 2, ara h 3, and ara h 6, or a derivative or part thereof having at least 70% sequence identity thereto. 
     
     
         8 . The poxvirus vector of  claim 1 , wherein the fusion protein comprises an amino acid sequence set out in SEQ ID NO: 12 or a derivative or part thereof having at least 70% sequence identity thereto. 
     
     
         9 . The poxvirus vector of  claim 1 , wherein the poxvirus vector comprises the nucleic acid sequence set out in one of SEQ ID NO: 11 or a derivative or part thereof having at least 70% sequence identity thereto. 
     
     
         10 . The poxvirus vector of  claim 1 , wherein the nucleic acid sequence encodes a fusion protein comprising peanut allergens ara h 1, ara h 2, ara h 3 and ara h 6. 
     
     
         11 . The poxvirus vector of  claim 1 , wherein the poxvirus vector is a vaccinia vector. 
     
     
         12 . The poxvirus vector of  claim 11 , wherein the poxvirus vector is a modified vaccinia vector or an avipox vector. 
     
     
         13 . The poxvirus vector of  claim 1 , comprising a pharmaceutically or physiologically acceptable carrier and/or diluent. 
     
     
         14 . A method of inducing tolerance to or suppressing an allergic response in a subject or patient, the method comprising administering to the subject or patient an effective amount of the poxvirus vector of  claim 1  for a time and under conditions sufficient to elicit suppression/tolerance. 
     
     
         15 . A method of vaccinating a subject to induce tolerance to a peanut allergen, comprising administering the poxvirus vector of  claim 1 . 
     
     
         16 . A method of desensitizing or inducing tolerance in a subject to a peanut allergen, the method comprising:
 i) collecting lymphocytes from the subject;   ii) co-culturing the lymphocytes with a cell transfected with the poxvirus vector of  claim 1  ex vivo to generate and/or expand a T H 1 lymphocyte population that recognizes the proteasomally degraded peanut allergen fusion protein associated with MHC Class I molecules on the cell; and   iii) administering the T H 1 lymphocyte population from (ii) to the subject.