ENHANCEMENT OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) BY DNA IMMUNIZATION WITH MYELIN PROTEOLIPID PROTEIN (PLP) PLASMID DNA

Relapsing-remitting experimental allergic encephalomyelitis (R-EAE) is an animal model for multiple sclerosis (MS). Many potential immunomod ulatory strategies for MS have been used first in EAE to assess their effectiveness. Recently, the injection of plasmid DNA has been shown t o induce potent humoral and cellular immune responses. The primary aim of our experiments reported here was to determine if vaccination with cDNAs encoding myelin proteolipid protein (PLP) could prime for a PLP -specific immune response and affect subsequent R-EAE. We constructed cDNAs encoding whole PLP (pPLP(all)) or encephalitogenic epitopes PLP1 39-151 (pPLP(139-151)) and PLP178-191 (pPLP(178-191)). Following DNA i njection, we induced R-EAE in SJL/J mice using PLD139-151 or PLP178-19 1 peptides in adjuvant. All 3 plasmid constructs enhanced R-EAE induce d with PLP139-151, and injection of mice with pPLP(all) increased R-EA E induced with PLPall DNA immunization induced higher PLP peptide-spec ific lymphoproliferative responses than did vector alone following R-E AE induction with IgG1 or IgG2b antibody responses. These data suggest that DNA immunization of PLP can modulate immune responses, leading t o enhancement of R-EAE.