MODIFIED TNF א MOLECULES CAPABLE OF RAISING NEUTRALIZING ANTIBODIES TOWARDS WILD TYPE HUMAN TNF a, DNA ENCODING SUCH MODIFIED TNF α MOLECULES AND VACCINES COMPRISING SUCH MODIFIED TNF α MOLECULES AND DNA

摘要

A modified human TNFα molecule capable of raising neutralizing antibodies towards wild-type human TNFα following administration of said modified TNFα molecule to a human host, wherein at least one peptide fragment of the human TNFα molecule has been substituted by at least one peptide known to contain an immunodominant T cell epitope or a truncated form of said molecule containing an immunodominant epitope and one or both flanking regions of the human TNFα molecule comprising at least one TNFα B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of the front β-sheet, in any one of the connecting loops and/or in any one of the B', I or D strands of the back β-sheet. The modified human TNFα molecules or DNA encoding them may be formulated as vaccines against TNFα optionally with pharmaceutically acceptable adjuvants, for the prevention or treatment of chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel diseases, cancer, disseminated sclerosis, diabetes, psoriasis, osteoporosis or asthma. Human body fluids may be tested for the presence of TNFα by contact with a composition containing the modified TNFα.