Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis

Vaccination with naked DNA represents a therapeutic strategy currently unde r consideration in multiple sclerosis (MS). In this study, we tested the po tential therapeutic effect of vaccination with a naked DNA construct encodi ng proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensiti zation for experimental autoimmune encephalomyelitis (EAE) actively-induced in Sn mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local mus cle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, ex acerbated form of disease tin comparison to control mice), while late sensi tization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a T h1-type cytokine response was noted. In contrast, sensitization >10 weeks p ost-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity. (C) 2000 P ublished by Elsevier Science B.V.