Increased DNA vaccine delivery and immunogenicity by electroporation in vivo

DNA vaccines have been demonstrated to be potent in small animals but are l ess effective in primates. One limiting factor may be inefficient uptake of DNA by cells in situ, In this study, we evaluated whether cellular uptake of DNA was a significant barrier to efficient transfection in vivo and subs equent induction of immune responses. For this purpose, we used the techniq ue of electroporation to facilitate DNA delivery in vivo. This technology w as shown to substantially increase delivery of DNA to cells, resulting in i ncreased expression and elevated immune responses. The potency of a weakly inmunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as se en by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In a ddition, the inmunogenicity of a potent HIV gag DNA vaccine was increased i n mice, as seen by higher Ab titers, a substantial reduction in the dose of DNA required to induce an Ab response, and an increase in CD8(+) T cell re sponses. Finally, Ab responses were enhanced by electroporation against bot h components of a combination HIV gag and env DNA vaccine in guinea pigs an d rabbits. Therefore, cellular uptake of DNA is a significant barrier to tr ansfection in vivo, and electroporation appears able to overcome this barri er.