Variants of group 6 allergens of the true grasses having reduced allergeneity due to mutagenesis of proline residues

Abstract

The present invention relates to the preparation and use of recombinant variants of group 6 allergens of the Poaceae (true grasses), which are characterised by reduced IgE reactivity compared with known wild-type allergens and at the same time substantially retained reactivity with T-lymphocytes.

1 . Hypoallergenic variant of a group 6 allergen of the true grass family (Poaceae) in which the prolines which correspond in an alignment to the prolines in positions 29, 30, 57, 79 in the amino acid sequence of wild-type Phl p 6 have mutated singly or in combinations. 
     
     
         2 . Hypoallergenic variant according to  claim 1 , characterised in that the group 6 allergen is Phl p 6. 
     
     
         3 . Hypoallergenic variant according to  claim 1 , characterised in that it is a fragment or variant of a hypoallergenic variant according to  claim 1  or a multimer of one or more hypoallergenic variants according to  claim 1  or characterised in that one or more hypoallergenic variants according to  claim 1  or fragments, variants or multimers thereof are a constituent of a recombinant fusion protein. 
     
     
         4 . DNA molecule which encodes for a hypoallergenic variant according to  claim 1 . 
     
     
         5 . Recombinant expression vector containing a DNA molecule according to  claim 4  functionally connected to an expression control sequence. 
     
     
         6 . Non-human host organism transformed by means of a DNA molecule according to  claim 4 . 
     
     
         7 . Process for the preparation of a hypoallergenic variant according to  claim 1  by cultivation of a non-human host organism transformed by a DNA molecule which encodes for the variant, and isolation of the corresponding allergen variant from the culture. 
     
     
         8 . Hypoallergenic variant according to  claim 1  as medicament. 
     
     
         9 . DNA molecule according to  claim 4  as medicament. 
     
     
         10 . Recombinant expression vector according to  claim 5  as medicament. 
     
     
         11 . A method for the prevention and/or therapeutic treatment of type 1 allergies in the triggering of which group 6 allergens of the true grasses are causally involved, comprising administering a medicament according to  claim 9 . 
     
     
         12 . Use of at least one DNA molecule according to  claim 4  for the preparation of a medicament for immunotherapeutic DNA vaccination. 
     
     
         13 . Pharmaceutical preparation comprising at least one hypoallergenic variant according to  claim 1  and optionally further active compounds and/or assistants for the prevention and/or therapeutic treatment of type 1 allergies. 
     
     
         14 . Pharmaceutical preparation according to  claim 13 , characterised in that the further active compounds are allergens of the true grasses or variants thereof.