Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen

Abstract

Direct gene transfer by intramuscular injection of plasmid DNA encoding an antigenic protein may be used for the purpose of immunization. DNA-based immunization may be of value for basic immunological research and vaccine development. 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 diffusion of the DNA within the muscle tissue or its entry into the muscle fibres. Although the efficiency of gene transfer in normal mouse muscle is low (< 100 fibres per injection site), a humoral response to the hepatitis B surface antigen (HBsAg) is obtained after expression of a transferred gene. Direct gene transfer is ten times more efficient in regenerating than in normal mouse muscle. DNA-based immunization in such regenerating muscles results in an earlier and stronger humoral response to HBsAg than is seen in normal mature muscle. A needleless jet injection system (Biojector ®) is able to deliver DNA into normal muscle in rats and rabbits such that a su