Modulation of antigen immunogenicity by deleting epitopes recognized by nkt cells

Abstract

The invention describes a method and compounds for the prevention of immune responses towards allofactors, towards viral vectors used for gene therapy and gene vaccination, towards proteins to which subjects are naturally exposed, towards genetically-modified organisms and towards undesirable effects related to vaccine administration for allergic or infectious diseases.

1 .- 14 : (canceled) 
     
     
         15 . An engineered peptide derived from a peptide selected from the group consisting of an allofactor, a viral vector, a genetically-modified organism and a vaccine for an allergen, the peptide naturally comprising an epitope comprising hydrophobic amino acid residues in position P1 and/or P7 and the peptide being capable of binding to CD1d molecule and/or activating NKT cells, the engineered peptide having been modified to eliminate said epitope by substituting hydrophobic amino acid residues in position P1 and/or P7 with a non-hydrophobic residue, so that the binding to CD1d molecule is reduced in the engineered peptide as compared with the peptide. 
     
     
         16 . The engineered peptide of  claim 15 , wherein the peptide comprises one or more motif consisting of [FWTHY]-X2X3-[ILMV]-X5X6-[FWTHY] and wherein the peptide has been modified to eliminate the [FWTHY] amino acids at positions P1 and/or P7 of the motif comprised in the peptide by substitution of the [FWTHY] amino acid by an amino acid different from [FWTHY]. 
     
     
         17 . The engineered peptide of  claim 15 , further comprising a substitution of the amino acid [ILMV] at position P4. 
     
     
         18 . The engineered peptide of  claim 15 , wherein the engineered peptide is derived from human adenovirus 5. 
     
     
         19 . The engineered peptide of  claim 18 , comprising a variant of one or more or all of the sequences: FIGLMYY, FDSICLY, FKKVAIT, FTRLKTK, WFLVQM, FMSMGAL and FDVVRVH. 
     
     
         20 . The engineered peptide of  claim 19 , wherein the engineered peptide is derived from Mal d 1. 
     
     
         21 . The engineered peptide of  claim 19 , comprising a variant of the sequence FKLIESY. 
     
     
         22 . The engineered peptide of  claim 15 , wherein the engineered peptide is derived from alpha-gliadin. 
     
     
         23 . The engineered peptide of  claim 22 , comprising a variant of the sequence YLQLQPF and/or the sequence FEEIRNL. 
     
     
         24 . The engineered peptide of  claim 15 , wherein the engineered peptide is derived from Derlp. 
     
     
         25 . The engineered peptide of  claim 24 , comprising a variant of one or more or all of the sequences: FSGVAAT, HSAIAVI and YPYVVIL. 
     
     
         26 . The engineered peptide of  claim 15 , wherein the engineered peptide is derived from an IgG. 
     
     
         27 . The engineered peptide of  claim 26 , comprising a variant of one or more or all of the sequences: YRVVSVL, FRVVSVL and HEALHNH.