RECOMBINANT ALLERGEN WITH REDUCED lgE BINDING BUT UNDIMINISHED T-CELL ANTIGENICITY

Abstract

The present invention relates generally to reagents useful in the immunotherapeutic or immunoprophylactic treatment of allergic diseases. More particularly, the present invention provides modified allergens exhibiting reduced IgE interactivity including reduced IgE production-stimulatory activity, while retaining T-cell antigenicity, which are useful in the immunomodulation of type I allergic disease conditions. The present invention further contemplates a method of immunomodulation of allergic diseases such as type I allergic disease conditions by the administration of modified allergens exhibiting reduced IgE interactivity while retaining T-cell antigenicity.

1 - 29 . (canceled) 
     
     
         30 . A protein allergen variant selected from the group consisting of an Lol p 5 protein allergen variant, a Phl p 5 protein allergen variant and a  Poa  p 5 protein allergen variant, wherein the variant comprises a naturally occurring Lol p 5, Phl p 5 or  Poa  p 5 protein allergen comprising (i) mutations K->N, F->L, T->A, V->A in amino acid residues homologous to the amino acid residues K172, F173, T174 and V175 of SEQ ID NO: 1 or (ii) mutations A->G, V->A, K->A in amino acid residues homologous to the amino acid residues A204, V205 and K206 of SEQ ID NO: 1. 
     
     
         31 . The protein allergen variant of  claim 30 , wherein one or more further IgE epitopes are mutated or deleted thereby increasing the hypoallergenicity of the allergen variant as compared to a naturally occurring Lol p 5, Phl p 5, or  Poa  p 5. 
     
     
         32 . The allergen variant of  claim 30 , wherein said protein allergen in naturally occurring form is associated with type I allergic disease in sensitive subjects. 
     
     
         33 . The allergen variant of  claim 32 , wherein the type I allergic disease is sensitivity to rye grass pollen. 
     
     
         34 . The allergen variant of  claim 32 , wherein said sensitive subject is a human, a primate, livestock animal, laboratory test animal or companion animal. 
     
     
         35 . The allergen variant of  claim 34 , wherein said sensitive subject is a human. 
     
     
         36 . A composition comprising the allergen variant according to  claim 30  and one or more pharmaceutically acceptable carriers and/or diluents. 
     
     
         37 . A method for the prophylaxis or treatment of an allergic disease or condition comprising administering the allergen variant of  claim 30  to a human or animal in need thereof. 
     
     
         38 . The protein allergen variant of  claim 30 , wherein the naturally occurring Lol p 5 protein allergen comprises the amino acids of SEQ ID NO: 1 or SEQ ID NO: 2, the naturally occurring Phl p 5 protein allergen comprises the amino acids of SEQ ID NO: 3 or SEQ ID NO: 4 and the naturally occurring  Poa  p 5 protein allergen comprises the amino acids of SEQ ID NO: 5 or SEQ ID NO: 6. 
     
     
         39 . The protein allergen variant of  claim 31 , wherein the variant comprises mutations K->N, F->L, T->A, V->A of (i) and wherein the one or more mutations or deletions comprise a mutation K->A in an amino acid residue homologous to the amino acid residue K57 of SEQ ID NO: 1 and mutations G->A, K->A in amino acid residues homologous to the amino acid residues G273 and K275 of SEQ ID NO: 1. 
     
     
         40 . The protein allergen variant of  claim 31 , wherein the variant comprises mutations A->G, V->A, K->A of (ii) and wherein the one or more mutations or deletions comprise a mutation K->A in an amino acid residue homologous to the amino acid residue K57 of SEQ ID NO: 1 and mutations G->A, K->A in amino acid residues homologous to the amino acid residues G273 and K275 of SEQ ID NO: 1. 
     
     
         41 . The protein allergen variant of  claim 31 , wherein the variant comprises mutations K->N, F->L, T->A, V->A of (i) and wherein the one or more mutations or deletions comprise a mutation K->A in an amino acid residue homologous to the amino acid residue K57 of SEQ ID NO: 1 and a deletion of an amino acid residue homologous to the amino acid residue G272 of SEQ ID NO: 1. 
     
     
         42 . The protein allergen variant of  claim 37 , wherein the variant comprises mutations A->G, V->A, K->A of (ii) and wherein the one or more mutations or deletions comprise a mutation K->A in an amino acid residue homologous to the amino acid residue K57 set forth in SEQ ID NO: 1 and a deletion of the amino acid residue homologous to amino acid residue G272 of SEQ ID NO: 1. 
     
     
         43 . The protein allergen variant of claim  44  comprising amino acids 26-301 of SEQ ID NO: 11 or amino acids 26-301 of SEQ ID NO: 12.