Nathan Karin, Sawsan Youssef and Gizi Wildbaum
Department of Immunology & Rappaport Institute for Medical Sciences. Rappaport Faculty of Medicine. Technion. Haifa. Israel.

We have recently used a modification of gene therapy (naked DNA vaccination) to induce immunological memory against self-proinflammatory chemokines such as MIP-1a or MCP-1. In these experiments animals were subjected to a repeated administration of different chemokine encoding DNA constructs together with a repeated immunostimulatory sequince (ISS). Under these conditions immunological memory to the product of each gene was established. Upon induction of experimental autoimmune encephalomyelitis (EAE), a T cell mediated autoimmune disease of the central nervous system that serves as a model for Multiple Sclerosis (MS), this memory was "turned on" to provide DNA vaccinated animals a high state of disease resistance. Antibodies to the product of each inserted gene were isolated form these animals. Each antibody was found to be neutralizing in vitro and capable of transferring disease resistance. Interestingly, the level of their production was dependent on disease severity and accelerated in accordance with disease progression. Thus, by using a simple gene therapy technique the immune system could be "re-educated" to restrain its own harmful activities.