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Methylated CpG‐Containing Plasmid Activates the Immune System
Author(s) -
Cornélie S.,
PoulainGodefroy O.,
Lund C.,
Vendeville C.,
Ban E.,
Capron M.,
Riveau G.
Publication year - 2004
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.0300-9475.2004.01373.x
Subject(s) - plasmid , cpg site , biology , dna , cpg oligodeoxynucleotide , plasmid preparation , microbiology and biotechnology , dna methylation , recombinant dna , immune system , methylation , gene , genetics , gene expression , pbr322
Bacterial DNA differs from mammalian DNA by the presence of unmethylated cytosine–phosphate–guanosine (CpG) motifs. The immunostimulatory properties of a DNA vaccine have been suspected to be associated with these motifs. The aim of this study was to assess the inactivation of the immunostimulatory potential of a plasmid after methylation of its CpG motifs. We constructed two identical non‐coding plasmids, and one of these was de novo methylated on its CG sequences. A single administration of recombinant antigen with methylated or unmethylated CpG‐containing plasmid was performed in mice. As expected, only unmethylated CpG‐containing plasmid enhanced the specific immune response. However, a study of in vivo activation of Langerhans' cells and analysis of mRNA synthesis indicated that both the plasmids promoted cell emigration and cytokine induction. These data highlight that a methylated CpG‐containing plasmid is not inert and carries immunomodulatory properties. The results further emphasize the necessity to definitively identify the mode of action of plasmids used for DNA vaccination.