Abstract: The present invention provides for an immunogenic analogue of a human TNF? protein, wherein said analogue comprises an immunogenized monomeric TNF? polypeptide or TNF? di- or timer, and wherein the analogue further comprises a toxicity reducing or abolishing mutation selected from the group consisting of Y87S, D143N or A145R, the amino acid numbering setting out from the N-terminal valine in human TNF?. The invention also provides for a nucleic acid fragment encoding the analogue as well as to vectors and transformed cells useful in the preparation of the analogue. Also disclosed are methods of down-regulating TNF? in a subject in need thereof.

Abstract: The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF&agr;). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF&agr; variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.

Abstract: The present invention relatas to novel immunogenic variants of multimeric proteins such as immunogenic variants of interleukin 5 (IL5) and tumour necrosis factor alpha (TNF, TNF&agr;). The variants are, besides from being immunogenic in the autologous host, also highly similar to the native 3D structure of the proteins from which they are derived. Certain variants are monomeric mimics of the multimers, where peptide linkers (inert or T helper epitope containing) ensure a spatial organisation of the monomomer units that facilitate correct folding. A subset of variants are monomer TNF&agr; variants that exhibit a superior capability of assembling into multimers with a high structural similarity to the native protein. Also disclosed are methods of treatment and production of the variants as well as DNA fragments, vectors, and host cells.