近期的《自然—材料學(xué)》報(bào)道了一種用聚合物材料制成的疫苗“補(bǔ)丁”,可以應(yīng)用于皮膚上,,將DNA疫苗簡(jiǎn)單地輸送入人體,。
Darrell Irvine, Paula Hammond等人發(fā)現(xiàn)將微型針頭與聚電解質(zhì)多層技術(shù)結(jié)合,可增強(qiáng)DNA疫苗的投遞效果,。這與利用生物試劑實(shí)現(xiàn)的DNA聯(lián)合投遞達(dá)到的效果一樣,,都能提高細(xì)胞中核酸的攝入量。這種“補(bǔ)丁”的聚合物微型針頭被用于皮膚上,,將加載疫苗的可生物降解聚電解質(zhì)薄膜植入皮膚表層,。與皮膚接觸的那層聚合物在應(yīng)用過(guò)程中會(huì)發(fā)生溶解,使得微型針頭能快速方便地被移除,。被植入的薄膜則釋放DNA與免疫刺激RNA到皮膚內(nèi),,這一釋放過(guò)程的持續(xù)時(shí)間是可調(diào)節(jié)的,可從數(shù)天到數(shù)周,。
這種采用微型針頭的多層技術(shù)所引發(fā)的免疫反應(yīng)能大大超過(guò)DNA疫苗的直接注射,。此外,這種含有微型針頭的補(bǔ)丁可在室溫干燥環(huán)境下儲(chǔ)存數(shù)周之久,,而不會(huì)失去活性,。由于其不需要冷藏技術(shù)且內(nèi)嵌的生物試劑在長(zhǎng)時(shí)間內(nèi)能保持活性,因此,這種疫苗補(bǔ)丁很適合于全球范圍的輸送,。(生物谷Bioon.com)
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Polymer multilayer tattooing for enhanced DNA vaccination
Peter C. DeMuth, Younjin Min, Bonnie Huang, Joshua A. Kramer, Andrew D. Miller, Dan H. Barouch, Paula T. Hammond & Darrell J. Irvine
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.