Plasmid-mediated delivery of antigens or biological response modifiers as means to suppress autoimmunity
The discovery of immunostimulatory motifs on bacterial DNA energized many laboratories, since it became evident that the associated Th1-driving ability is a positive feature, optimizing the quality of plasmid vectors as antiviral or antiallergic vaccines. In fact, the Thl adjuvant activity of unmethylated CpG motifs can be even used to circumvent the inherently low and Th2-biased responsiveness of neonates. With all the advances during the last decade that promoted the initiation of clinical trials with DNA vaccines, a limiting factor was still the low magnitude of immunity.
KeywordsExperimental Autoimmune Encephalomyelitis Glutamic Acid Decarboxylase Biological Response Modifier Genetic Immunization Rheumatoid Arthritis Model
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- Bronte V, Appoloni E, Ronca R, Zamboni P, Overwijk WW, Surman L, Restifo NP, Zanovello P (2000) Genetic vaccination with self tyrosinase-related protein 2 caused melanoma eradication but not vitiligo. Cancer Res 15: 253–258Google Scholar
- Lobell A, Weissert R, Storch MK, Svanholm C, de Graaf KL, Lassmann H, Andersson R, Olsson T, Wigzell H (1998) Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc of immunoglobulin G suppresses experimental autoimmune encephalomyelitis. J Exp Med 187: 1543–1548PubMedCrossRefGoogle Scholar
- Tsunoda I, Kuang LQ, Tolley ND, Whitton JL, Fujinami RS (1998) Enhancement of experimental allergic encephalomyelitis (EAE) by immunization with myelin proteolipid protein (PLP) plasmid DNA. J Neuro-pathol Exp Neurol 57: 758–767Google Scholar
- Weissert R, Lobell A, de Graaf KL, Eltayeb SY, Andersson R, Olsson M, Wigzell H (2000) Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen. Proc Natl Acad Sci USA 97: 1689–1694PubMedCrossRefGoogle Scholar
- Wildbaum G, Youssef S, Karin N (2000a) A targeted DNA vaccine augments the natural immune response against TNF-alpha and suppresses ongoing adjuvant arthritis. J Immunol 165: 5860–5866Google Scholar