DNA vaccination is an important new concept which is rapidly gaining acceptance as both a viable and potentially superior alternative to the use of traditional purified antigen and attenuated viruses. Due to enzymatic and mucosal barriers, oral delivery of plasmids for DNA vaccine applications has remained largely unexplored. Nonetheless, the possibility of targeting the gut associated lymphoid tissue (GALT) via the Peyer's patches, an important site for induction of both systemic and mucosal immunity, provides a compelling rationale for development. Utilizing the biological phenomenon of particle uptake, we have developed a thermoplastic, bioadhesive, 'nano-sized' microsphere system capable of delivering plasmid DNA into the Peyer's patches following oral administration. The technical objectives of this proposal focus on establishing proof of principle that microencapsulation of DNA provides a pathway for oral delivery of genes, specifically for DNA vaccine applications. A HIV DNA vaccine prototype will be encapsulated into poly fumaric-co-sebacic acid (FA:SA) microspheres using a proprietary technique, phase inversion nanoencapsulation (PIN). Microspheres encapsulating HIV DNA vaccine candiate will be fed to mice and resulting immune response (serum IgG, vaginal/fecal IgA) will be measured by ELISA. The development of this platform fulfills the need for an effective technique to deliver DNA into alternative tissues and provides the opportunity to expand DNA vaccination to target diseases where mucosal immunity is critical.
The oral route is the simplest route for administration of therapeutic compounds. The development of an oral delivery system for DNA vaccination fulfills the need for an effective technique to deliver DNA into mucosal tissue sites.
| Zinckgraf, John W; Silbart, Lawrence K (2003) Modulating gene expression using DNA vaccines with different 3'-UTRs influences antibody titer, seroconversion and cytokine profiles. Vaccine 21:1640-9 |
