M. Sela

Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy rises. Efforts to develop such vaccines against cancer, AIDS, hepatitis, tuberculosis, Alzheimers disease, mad cow disease, etc. have not yet reached the stage where they can be successfully used on a daily basis. But in the realm of autoimmune diseases, significant progress has been made, resulting, at least in one case, in an immunomodulatory vaccine against multiple sclerosis, developed in our laboratory, which is in daily use by about 100,000 patients. The drug, or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis, is a copolymer of four amino acid residues, denoted Copaxone, related to myelin basic protein. In this presentation we shall discuss Copaxone, as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor.

Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer, immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans, and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-?-subunit, p195-212 and p259-271, are immunodominant T cell epitopes in MG patients and in two strains of mice. Altered peptide ligand, composed of the tandemly arranged two single amino acid analogs, inhibits in vitro and in vivo MG-associated autoimmune responses. The active suppression is mediated by the CD4+CD25+ immunoregulatory cells and is associated with the down-regulation of Th1-type cytokines and the up-regulation of the secretion of IL-10 and the immunosuppressive cytokine, transforming growth factor beta.

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