HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Widera, G. Articles by Ulmer, J. B. Search for Related Content PubMed PubMed Citation Articles by Widera, G. Articles by Ulmer, J. B.

Increased DNA Vaccine Delivery and Immunogenicity by Electroporation In Vivo

Georg Widera, Melissa Austin, Dietmar Rabussay, Cheryl Goldbeck^*, Susan W. Barnett^*, Minchao Chen^*, Louisa Leung^*, Gillis R. Otten^*, Kent Thudium^*, Mark J. Selby^* and Jeffrey B. Ulmer^1,*

^* Vaccines Research, Chiron Corporation, Emeryville, CA 94608; and Genetronics, Inc., San Diego, CA 92121

DNA vaccines have been demonstrated to be potent in small animals but are less 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 subsequent induction of immune responses. For this purpose, we used the technique of electroporation to facilitate DNA delivery in vivo. This technology was shown to substantially increase delivery of DNA to cells, resulting in increased expression and elevated immune responses. The potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as seen by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag DNA vaccine was increased in 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 responses. Finally, Ab responses were enhanced by electroporation against both components of a combination HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore, cellular uptake of DNA is a significant barrier to transfection in vivo, and electroporation appears able to overcome this barrier.