Use of plasmid DNA for direct gene transfer and immunization.
Direct gene transfer by intramuscular injection of plasmid DNA encoding an antigenic protein may be used for the purpose of immunization. Several factors influence the uptake and expression of plasmid DNA in skeletal muscle, which in turn influence the immune response to the expressed protein. Physical barriers and other factors may impede the diffusion of the DNA within the muscle tissue or its entry into the muscle fibers. Although the efficiency of gene transfer in normal mouse muscle is low (< 100 fibers per injection site), both humoral and cell-mediated immune responses to the hepatitis B surface antigen (HBsAg) are obtained after the expression of a transferred gene, and these are dose dependent. The efficacy of the immune response can be improved by injection of the DNA in or following pretreatment with a hypertonic solution or with the local anesthetic bupivacaine, and even more so by injecting the DNA into regenerating muscle.
Davis
H L
HL
Loeb Medical Research Institute, Ottawa Civic Hospital, Canada.
Michel
M L
ML
Whalen
R G
RG
D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006801:Humans; D006982:Hypertonic Solutions / Q000008:administration & dosage; D007114:Immunization / Q000379:methods*; D007273:Injections, Intramuscular; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012038:Regeneration; D014162:Transfection / Q000379:methods*
D004274:DNA, Recombinant; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006982:Hypertonic Solutions; D011994:Recombinant Proteins; D002045:Bupivacaine