Laser mimicking mosquito bites for skin delivery of malaria sporozoite vaccines.
Laser mimicking mosquito bites for skin delivery of malaria sporozoite vaccines.
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激光模拟蚊子叮咬，用于皮肤输送疟疾子孢子疫苗。
DOI：
10.1016/j.jconrel.2015.02.031
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wu,MeiX
中科院分区：
文献类型：
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作者：
Zhou,Chang;Chen,Xinyuan;Zhang,Qi;Wang,Ji;Wu,MeiX
通过蚊子叮咬进行辐射减毒子孢子（RAS）免疫已被证明可以在人类中诱导针对疟疾的无菌免疫力，但这种疫苗接种途径既不实用也不道德。最近的人体研究证实了通过循环将 RAS 输送至肝脏以引发针对这种寄生虫的免疫力的重要性，表明只有通过静脉 (IV) 注射 RAS 才能实现高水平的保护，而不是通过皮内 (ID) 或皮下 (SC) 疫苗接种。在这里，我们在小鼠模型中报告，将 RAS 注射到激光照射的皮肤中，可提供针对疟疾感染的免疫保护，几乎与静脉注射免疫一样有效。由于血红蛋白对光的特异性吸收，用低功率 532 nm Nd:YAG 激光短暂照射接种部位可增强皮肤下方毛细血管的渗透性。血管通透性的增加似乎通过一种尚不清楚的机制促进了 RAS 与血管壁的结合，最终促进 RAS 进入循环系统并到达肝脏的量比 ID 给药增加了 7 倍。因此，在激光治疗部位进行 RAS 的 ID 免疫比 ID 疫苗接种刺激了更强的子孢子特异性抗体和 CD8+IFN-γ+T 细胞反应，并提供了几乎完全的针对疟疾感染的保护，而单独的 ID 免疫是无效的。这种新颖、安全且方便的策略可增强 ID 子孢子疫苗的功效，值得在大型动物和人类中进行进一步研究。
Immunization with radiation-attenuated sporozoites (RAS) via mosquito bites has been shown to induce sterile immunity against malaria in humans, but this route of vaccination is neither practical nor ethical. The importance of delivering RAS to the liver through circulation in eliciting immunity against this parasite has been recently verified by human studies showing that high-level protection was achieved only by intravenous (IV) administration of RAS, not by intradermal (ID) or subcutaneous (SC) vaccination. Here, we report in a murine model that ID inoculation of RAS into laser-illuminated skin confers immune protection against malarial infection almost as effectively as IV immunization. Brief illumination of the inoculation site with a low power 532 nm Nd:YAG laser enhanced the permeability of the capillary beneath the skin, owing to hemoglobin-specific absorbance of the light. The increased blood vessel permeability appeared to facilitate an association of RAS with blood vessel walls by an as-yet-unknown mechanism, ultimately promoting a 7-fold increase in RAS entering circulation and reaching the liver over ID administration. Accordingly, ID immunization of RAS at a laser-treated site stimulated much stronger sporozoite-specific antibody and CD8+IFN-γ+T cell responses than ID vaccination and provided nearly full protection against malarial infection, whereas ID immunization alone was ineffective. This novel, safe, and convenient strategy to augment efficacy of ID sporozoite-based vaccines warrants further investigation in large animals and in humans.