Prevention of experimental autoimmune encephalomyelitis by MIP-1alpha and MCP-1 naked DNA vaccines.
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS). RT-PCR verified by Southern blotting and sequencing of PCR products of two C-C chemokines, MIP-1alpha and MCP-1, was performed on brain samples from EAE rats to evaluate mRNA transcription of these chemokines at different stages of disease. mRNA transcription in of each chemokine peaked after the onset of disease and declined during its remission. Each PCR product was then used as a construct for naked DNA vaccination. The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines prevented EAE. Immunization of CFA without the encephalitogenic epitope did not elicit an 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.
Youssef
S
S
Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, 31096, Israel.
Wildbaum
G
G
Karin
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics; D015551:Autoimmunity; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D066298:In Vitro Techniques; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D014158:Transcription, Genetic; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*
D000941:Antigens; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D019444:Vaccines, DNA