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During somatic
gene therapy experiementation in mice e.g. for muscular dystropy it was found that naked
plasmid DNA injected into the muscle produced immunogenic foreign protein rather
like a replicating virus. The injected animals then made a strong Tc response and some
antibody to the injected gene-product. The DNA, which is in the form of a naked circular
plasmid with a viral promoter in front of the vaccine gene, also acts as a proinflammatory
because the non-vertebrate DNA is a "danger" signal. Many antiviral DNA vaccines are now being tested using envelope genes as immunogen e.g.) for bovine herpes (at Saskatewan), BVDV (here at the RVC), for Feline immundeficiency virus (at Glasgow). Cytokine genes eg IL1 or IL18 or GMCSF are sometimes used to increase immungenicity and the uptake of DNA by dendritic cells. Safety issues, e.g. integration into animal or human chromosomes, may ban such DNA vaccines. Non-invasive routes of application of DNA ,e.g. eyedrops or skin patches, are being tested for horses re equine influenza at Wisconsin vet school.(ref Lunn et al, 1999 Antibody responses to DNA vaccination of horses., Vaccine, 17, 2245-58). Olsen's group are now using equine cytokines as immunopotentiators with such vaccines. |