Novel Polymer Film-Based Delivery System Enhances Potential of DNA Vaccines

A paper described a novel polymer film-based system for the time-release delivery of DNA vaccines.

DNA vaccines have many potential benefits but they failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination has not yet been developed.

In a new approach, investigators at the Massachusetts Institute of Technology (Cambridge, USA) implanted vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA (adjuvant), and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers.

Microneedle injections were deep enough to deliver the DNA to immune cells in the epidermis, but not deep enough to cause pain in the nerve endings of the dermis. After injection, contact with moisture caused the films to degrade and release the vaccine over a period of days or weeks. The amount of DNA delivered was determined by the number of polymer layers, while the rate of delivery was controlled by altering the hydrophobic properties of the film. An adjuvant consisting of RNA strands that resembled viral RNA provoked inflammation and recruited immune cells to the area.

Results published in the January 27, 2013, online edition of the journal Nature Materials revealed that films transferred into the skin of mice following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These "multilayer tattoo" DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than did intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.

"This type of vaccine delivery would also eliminate the need to inject vaccines by syringe," said senior author Dr. Darrell Irvine, professor of biological engineering and materials science and engineering at the Massachusetts Institute of Technology. "You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin. If you are making a protein vaccine, every protein has its little quirks, and there are manufacturing issues that have to be solved to scale it up to humans. If you had a DNA platform, the DNA is going to behave the same no matter what antigen it is encoding."

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Massachusetts Institute of Technology