| 摘要 |
An immunogenic composition comprises a peptide that induces in vivo TNF monomer-specific antibodies that bind an epitope of dissociated monomers of human TNF, the epitope being located wholly or partially within a TNF monomer-monomer interface region. Antibodies induced in vivo by this composition disrupt assembly or prevent re-assembly of the TNF monomers into bioactive trimeric human sTNF. The composition can comprise an additional peptide that induces in vivo TNF monomer- specific antibodies that bind another epitope of dissociated monomers of human TNF. Methods of making these immunogenic compositions are also described. Methods for treating a subject having a disease mediated by human TNF comprise administering a described immunogenic compositions which induces antibodies in a treated subject that disrupt or reduce the in vivo assembly or reassembly of dissociated monomers of TNF into bioactive trimeric human sTNF. These compositions and methods do not affect the structure or bioactivity of tmTNF or increase the treated subject's susceptibility to infection by an intracellular pathogen. |
