Process for the Preparation of Hypoallergenic Mosaic Antigens

Abstract

A process for the preparation of an hypoallergenic mosaic antigen derived from an allergen is disclosed whereby a) in a first step the allergen is split into at least two parts and the IgE reactivity of each part is determined and b) in a second step those parts of the allergen which have no detectable IgE reaction are combined to a mosaic antigen which comprises the amino acids of the allergen but the order of the amino acids of the mosaic antigen is different from that of the naturally occurring allergen.

1 . A process for the preparation of an hypoallergenic mosaic antigen derived from an allergen whereby
 (a) in a first step the allergen is split into at least two parts and the IgE reactivity of each part is determined and   (b) in a second step those parts of the allergen which have no detectable IgE reaction are combined to a mosaic antigen which comprises the amino acids of the allergen but the order of the amino acids of the mosaic antigen is different from that of the naturally occurring antigen.   
     
     
         2 . The process according to  claim 1  wherein in the first step at least two parts of the allergen are prepared by chemical synthesis or by using the polymerase chain reaction and each part of the allergen is separately reacted with serum obtained from allergic individuals and the reactivity of IgE antibodies contained within such serum with each part of the allergen is determined. 
     
     
         3 . The process according to  claim 1  wherein the order of the parts of the allergen having no substantial reactivity with IgE antibodies obtained from allergic individuals does not correspond with the order of those parts in the naturally occurring allergen insofar as the part naturally occurring at the N-terminus and the part normally occurring at the C-terminus are replaced by each other. 
     
     
         4 . The process according to  claim 1  wherein the allergen is a group 2 allergen. 
     
     
         5 . The process according to  claim 1  wherein the allergen is the timothy grass pollen allergen Phl p 2. 
     
     
         6 . The process according to  claim 5  wherein the allergen Phl p 2 is split into three peptides, namely peptide 1 having amino acids 1-33, peptide 2 having amino acids 34-64 and peptide 3 having amino acids 65-96 of the amino acid sequence of naturally occurring Phl p 2 and the mosaic antigen is provided by linking the peptides in the order peptide 1, peptide 3, peptide 2. 
     
     
         7 . (canceled) 
     
     
         8 . A DNA sequence comprising the nucleotide sequence of SEQ ID NO: 2 coding for the mosaic allergen of  claim 7  or a sequence complementary thereto. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . A vaccine for the treatment of grass pollen allergic patients characterized in that it comprises a DNA sequence coding for a mosaic antigen obtainable by a process according to  claim 1 , the DNA of  claim 8  or a sequences complementary to either of these DNA sequences. 
     
     
         15 . A method for treating an allergic reaction comprising administering a mosaic allergen obtainable by a process according  claim 1  to a subject in need thereof. 
     
     
         16 . The method of  claim 15  wherein the allergic reaction is caused by grass pollen. 
     
     
         17 . The method of  claim 15  wherein the allergic reaction is caused by timothy grass pollen. 
     
     
         18 . The method of  claim 15  wherein the allergic reaction is caused by timothy grass pollen allergen Phl p 2.