Long-term stability of influenza vaccine in a dissolving microneedle patch.
Long-term stability of influenza vaccine in a dissolving microneedle patch.
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DOI：
10.1007/s13346-016-0282-2
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发表时间：
2017-04
影响因子：
5.4
通讯作者：
Prausnitz, Mark R.
中科院分区：
文献类型：
--
作者：
Mistilis, Matthew J.;Joyce, Jessica C.;Esser, E. Stein;Skountzou, Ioanna;Compans, Richard W.;Bommarius, Andreas S.;Prausnitz, Mark R.
关键词：
本研究验证了一种假设，即优化的微针贴片配方可以在冷链外的长期储存期间以及在生产和储存过程中暴露于潜在压力时稳定三价亚单位流感疫苗。经ELISA检测，含有海藻糖/蔗糖、蔗糖/精氨酸和精氨酸/七氟糖酸盐组合的制剂在25°C保存长达24个月期间，成功地保留了大部分或全部疫苗活性。微针贴剂的最佳配方含有精氨酸/七糖葡酸盐，在研究期间没有显示出疫苗活性的显著丧失。为了验证这些体外研究结果，将储存在微针贴片中超过一年的三价流感疫苗在25°C下免疫小鼠，其抗体滴度大于或等于皮内注射的新鲜液体疫苗，表明在储存期间免疫原性保持不变。最后，在60°C环境下暴露4个月、多次冻融循环和电子束辐照下，微针贴片流感疫苗没有明显的活性丧失。我们得出的结论是，优化配方的微针贴片在冷链外的长时间储存和其他环境压力下仍能保持流感疫苗的活性，这表明微针贴片在药店货架上不冷藏储存的可能性。
This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25°C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than one year at 25°C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60°C for four months, multiple freeze-thaw cycles, and electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.
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DOI：
10.1086/649228
发表时间：
2010-01-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Kim YC;Quan FS;Yoo DG;Compans RW;Kang SM;Prausnitz MR
通讯作者：
Prausnitz MR
影响因子：
10.8
作者：
Choi, Hyo-Jick;Bondy, Brian J.;Prausnitz, Mark R.
通讯作者：
Prausnitz, Mark R.
影响因子：
3.4
作者：
Crowe, LM;Reid, DS;Crowe, JH
通讯作者：
Crowe, JH
影响因子：
5.8
作者：
McGrath, Marie G.;Vrdoljak, Anto;Crean, Abina M.
通讯作者：
Crean, Abina M.
影响因子：
3.8
作者：
Ameri, Mahmoud;Wang, Xiaomei;Maa, Yuh-Fun
通讯作者：
Maa, Yuh-Fun