Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis.

Abstract

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-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.

• Authors: K Selmaj, C Kowal, A Walczak, J Nowicka, C S Raine
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 111 Issue 1-2 Pg. 34-44 (Nov 01 2000) ISSN: 0165-5728 [Print] Netherlands
• PMID: 11063819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Myelin Proteolipid Protein
• Vaccines, DNA

Topics

• Animals
• Apoptosis (immunology)
• Autoantigens (immunology)
• Cell Division (immunology)
• Cytomegalovirus (genetics)
• Cytotoxicity Tests, Immunologic
• Demyelinating Diseases (immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology, prevention & control)
• Female
• Immunotherapy, Active
• Lymph Nodes (cytology)
• Mice
• Mice, Inbred Strains
• Multiple Sclerosis (immunology, pathology, prevention & control)
• Myelin Proteolipid Protein (genetics, immunology)
• Plasmids (immunology)
• Spinal Cord (immunology, pathology)
• T-Lymphocytes (cytology)
• Vaccines, DNA (immunology)