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*
Department of Immunology,
Rappaport Family Institute for Research in the Medical Sciences, and
Department of Morphological Sciences, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; and
§
Department of Hematology Rambam Medical Center, Haifa, Israel
DNA vaccination represents a novel means of expressing Ag in vivo
for the generation of both humoral and cellular immune responses. The
current study uses this technology to elicit protective immunity
against experimental autoimmune encephalomyelitis (EAE), a T
cell-mediated autoimmune disease of the central nervous system that
serves as an experimental model for multiple sclerosis. RT-PCR verified
by Southern blotting and sequencing of PCR products of four different
C-C chemokines, macrophage-inflammatory protein-1
(MIP-1),
monocyte-chemotactic protein-1 (MCP-1), MIP-1ß, and RANTES, were
performed on brain samples from EAE rats to evaluate mRNA transcription
at different stages of disease. Each PCR product was then used as a
construct for naked DNA vaccination. The subsequent in vivo immune
response to MIP-1 or MCP-1 DNA vaccines prevented EAE, even if
disease was induced 2 mo after administration of naked DNA vaccines. In
contrast, administration of the MIP-1ß naked DNA significantly
aggravated the disease. Generation of in vivo immune response to RANTES
naked DNA had no notable effect on EAE. MIP-1, MCP-1, and MIP-1ß
mRNA transcription in EAE brains peaked at the onset of disease and
declined during its remission, whereas RANTES transcription increased
in EAE brains only following recovery. Immunization of CFA without the
encephalitogenic epitope did not elicit the anti-C-C chemokine
regulatory response in DNA-vaccinated rats. Thus, modulation of EAE
with C-C chemokine DNA vaccines is dependent on targeting chemokines
that are highly transcribed at the site of inflammation at the onset of
disease.
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