Delivering DNA Vaccine by Transdermal Electroporation

摘要

Successful delivery of the HER-2/neu derived p369 peptide vaccine, KIFGSLAFL, to a large population of skin Langerhans cells (LC) by transdermal electroporationis expected to enhance the CTL response to breast cancer cells. Strategies have been developed to improve the electroporation protocol to enable the delivery of peptides. By using anionic lipids and detergents, the upper molecular weight limit of transdermal delivery by electroporation has been extended to beyond 10,000. This enables the delivery of antigenic peptides but not minigenes. With the new design of skin electrode, the transdermal flux of antigenic peptides was measured to be in the order of 10 mug/cm2/min. Electric pulses also stimulates the migration of skin Langerhans cells. Antigen-specific CTL response in immunized mice was measured by ELISPOT of gamma-interferon production. Earlier attempts to generate CTL response to KIFGSLAFL by electroporation delivery were negative, due to weak immune response. CTL response to electroporation delivery of the peptide vaccine SIINFEKL was positive, although it was not as effective as intradermal injection. We attribute the weaker response to the necessity to inject adjuvant separately. Effort to simultaneously deliver lower molecular weight CpG-containing oligonucleotide adjuvant by electroporation is underway. Delivery of p369 HER-2/ neu derived peptide vaccines will be re-examined.