Modified tnfalpha molecules, dna encoding such modified tnfalpha molecules and vaccines comprising such modified tnfalpha molecules and dna

摘要

A modified human TNFalpha molecule is capable of raising neutralizing antibodies towards unmodified human TNFalpha following administration of the modified TNFalpha to a human host, wherein one or more peptide fragments of the human TNFalpha molecule has been substituted by one or more peptides containing immunodominant T cell epitopes or a truncated form of the molecule containing the immunodominant epitope and one or both flanking regions of the human TNFalpha-molecule containing at least one TNFalpha B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of any one of the strands of the front beta-sheet, in any one of the connecting loops, or in any one of the B', I, or D strands of the back beta-sheet.