Dose sparing enabled by skin immunization with influenza virus-like particle vaccine using microneedles.

Dose sparing enabled by skin immunization with influenza virus-like particle vaccine using microneedles.
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DOI:
10.1016/j.jconrel.2010.07.125
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发表时间:
2010-11-01
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Kang SM
Kang SM
中科院分区:
其他
文献类型:
--
作者:
Quan FS;Kim YC;Compans RW;Prausnitz MR;Kang SM

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为了解决传统流感疫苗生产和交付的局限性,本研究调查了使用微针贴片的病毒样颗粒(VLP)流感疫苗的给药情况。目标是确定使用微针的流感VLP疫苗皮肤免疫是否能够节省剂量。我们发现,在小鼠模型中,使用微针的低剂量流感(A/PR/8/34 H1N1)VLP疫苗比低剂量肌肉注射(IM)疫苗具有更强的免疫原性,与高剂量IM疫苗的免疫原性相似。当疫苗剂量为1微克时,两种途径的免疫应答和保护效果相似,但微针接种更有效地诱导肺内的Recall抗体反应和骨髓中的抗体分泌细胞。在小剂量疫苗(0.3µg)下,微针免疫诱导了显著优越的保护性免疫,包括结合抗体和功能抗体,以及对大剂量致死性A/PR/8/34病毒的完全保护,而IM免疫只提供了部分保护(40%)。因此,本研究表明,皮肤内接种微针疫苗能在较低剂量下提供更有效的保护性免疫,从而提供疫苗剂量节约效应。
To address limitations of conventional influenza vaccine manufacturing and delivery, this study investigated administration of virus-like particle (VLP) influenza vaccine using a microneedle patch. The goal was to determine if skin immunization with influenza VLP vaccine using microneedles enables dose sparing. We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using microneedles was more immunogenic than low-dose intramuscular (IM) vaccination and similarly immunogenic as high-dose IM vaccination in a mouse model. With 1 µg dose of vaccine, both routes showed similar immune responses and protective efficacy, with microneedle vaccination being more effective in inducing recall antibody responses in lungs and antibody secreting cells in bone marrow. With a low dose of vaccine (0.3 µg), microneedle vaccination induced significantly superior protective immunity, which included binding and functional antibodies as well as complete protection against a high dose of lethal infection with A/PR/8/34 virus, whereas IM immunization provided only partial (40%) protection. Therefore, this study demonstrates that microneedle vaccination in the skin confers more effective protective immunity at a lower dose, thus providing vaccine dose sparing effects.
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