Modified human TNFalpha molecules, DNA encoding such altered TNFalpha molecules, and vaccines containing such altered TNFalpha molecules and DNA

摘要

New modified human tumour necrosis factoralpha , TNFalpha , (I) , able to generate, in humans, neutralising antibodies (Ab) to wild-type human TNFalpha (Ia): (a) has = 1 fragment of TNF substituted by a peptide containing an immunodominant T-cell epitope, or (b) is a truncated form of (a) containing an immunodominant epitope and one or both flanking regions of TNF, including = 1 TNFalpha B-cell epitope. The substitution causes a significant change in the amino acid (aa) sequence of any one of the strands in the front beta -sheet (fbS), any of the connecting loops and/or any of the B', I or D strands in the back beta -sheet (bbS). Also new are: (1) dimers, oligomers and multimers of (I); (2) isolated DNA (II) that encodes (I); (3) (expression) vectors containing (II); (4) hosts transformed with the expression vector, and (5) fusion proteins (FP) of (I) with an immunological adjuvant.