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Polymer multilayer tattooing for enhanced DNA vaccination.

ABSTRACT: DNA vaccines have many potential benefits but have 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 remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin 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 intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.

SUBMITTER: DeMuth PC

PROVIDER: S-EPMC3965298 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Polymer multilayer tattooing for enhanced DNA vaccination.

DeMuth Peter C PC Min Younjin Y Huang Bonnie B Kramer Joshua A JA Miller Andrew D AD Barouch Dan H DH Hammond Paula T PT Irvine Darrell J DJ

Nature materials 20130127 4

DNA vaccines have many potential benefits but have 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 remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coat ...[more]

PMID: 23353628

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Project description:Aerosol loading behavior of PVDF nanofiber electret filters using neutrally charged nano- and submicron aerosols was investigated experimentally for the first time. The loading behavior include variations of filtration efficiency and pressure drop and distribution of deposited aerosols in the filters all having the same fiber basis weight (3.060 gsm). Through the filtration efficiency variations of uncharged/charged, single-/multi-layer filters with aerosol loading, it was observed that mechanical PVDF filters had continuously increasing filtration efficiency, while PVDF electret filters had initially decreasing and subsequently increasing filtration efficiency until reaching 100% due to diminishing electrostatic effect and enhancing mechanical effect. By combining the pressure drop evolution of different filters during aerosol loading and detailed SEM images of the loaded filters, we have demonstrated that multilayer PVDF filters, especially the electret ones, could significantly slow down the pace of filter clogging (skin effect) and increase significantly the aerosol holding capacity during depth filtration. Generally, the multilayer nanofiber filters received the most aerosol deposit during depth filtration, whereas the single-layer nanofiber filters with the same basis weight of fibers received the most deposit during cake filtration. The multilayer nanofiber filters had approximately 70% aerosol deposit in the filter during depth filtration fully utilizing the full filter thickness, especially for the electret filters that had charged fibers, and only 30% deposit in the cake. On the contrary, the single-layer uncharged/charged nanofiber filters were exactly the reverse due to persistency of the skin effect with only 30% deposit in the filter mostly located in the upstream layer, yet 70% deposit in the cake. During depth filtration, the pressure drop per added mass deposit for the multilayer electret filter was very low at 11 Pa gsm-1, which was at least twice below any other nanofiber filters. This was all attributed to the uniform capture of aerosols by electrostatic effect across the entire filter depth from the upstream to downstream layers of the multilayer electret filter. The above conclusion was confirmed by the detailed SEM images taken across the different filter layers for the multilayer filter configuration. The 4-layer electret nanofiber filter with a 3.060-gsm basis weight has 4 times more aerosol holding capacity than the single uncharged/charged nanofiber filter with the same fiber basis weight in depth filtration. Based on the standpoint of highest efficiency and capacity with maximum pressure drop 800 Pa imposed on the filtration operation, the 4-layer nanofiber electret was the best among all 4 filters. It had 52% more aerosol holding capacity than the single layer uncharged nanofiber filter and 38% more capacity than the charged single-layer and the uncharged multilayer nanofiber filters. The multilayer PVDF electret filters have excellent filtration performance for long-term aerosol filtration and also great potential applications in the fields of personal health care and environmental protection.

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Polymer multilayer tattooing for enhanced DNA vaccination.

Publications

Polymer multilayer tattooing for enhanced DNA vaccination.

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