Wolf Prize Laureate in Medicine 1998
Affiliation at the time of the award:
Weizmann Institute of Science, Israel
“for their major discoveries in the field of immunology”.
Professors Michael Sela and Ruth Arnon were the first to introduce synthetic polypeptides into immunological research and insinuated the notion of immunogen and immunogenicity. They conceived the idea of synthetic vaccines as a mere concept in drug design and opened the road to the development of peptide vaccines. Their pioneering discoveries enabled safe, effective and long-term vaccines to be produced against infectious diseases, as well as specific peptides to be developed to treat autoimmune disorders.
Michael Sela and Ruth Arnon first introduced the use of linear and branched synthetic polypeptides as antigens, and thus brought about a better understanding of immunological phenomena. They have introduced then the notions of immunogen and immunogenicity. Distinguishing between sequential and conformational epitopes, they have succeeded to synthesize a peptide cross-linked by a disulfide bond, derived from native lysozyme. This synthetic conformational epitope, attached to a synthetic branched polypeptide, evoked antibodies reactive with the native protein. Based on this finding, Sela and Arnon developed the notion of synthetic vaccines against infectious diseases in which a specific epitope, as well as an adjuvant, could be linked covalently to a macromolecular carrier, leading to neutralizing antibodies. For close to 30 years Arnon and Sela have been deeply interested in the possibility of fighting the autoimmune disease, experimental allergic encephalomyelitis (EAE) with synthetic analogs of the molecules in the myelin sheath of the brain which are capable of provoking the disease.
Among the many analogs initially tested, they concentrated their efforts on a synthetic copolymer of four amino acids, denoted Cop 1, which cross-reacts immunologically both at the antibody level and at the T cell level, with the myelin basic protein (MBP). Cop 1 can suppress the onset of the disease in laboratory animals such as guinea pigs, rabbits, mice and rats, reverts the disease in monkeys, and is capable of reducing the number of attacks in patients with exacerbating-remitting type of multiple sclerosis (MS). Its development paves the way for the design of specific drugs for treatment of other autoimmune diseases, based on the nature of the respective autoantigen.