Intradermal immunization by Ebola virus GP subunit vaccines using microneedle patches protects mice against lethal EBOV challenge.

Intradermal immunization by Ebola virus GP subunit vaccines using microneedle patches protects mice against lethal EBOV challenge.
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DOI:
10.1038/s41598-018-29135-w
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发表时间:
2018-07-25
期刊:
影响因子:
4.6
通讯作者:
Yang C
Yang C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu Y;Ye L;Lin F;Gomaa Y;Flyer D;Carrion R Jr;Patterson JL;Prausnitz MR;Smith G;Glenn G;Wu H;Compans RW;Yang C

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开发一种安全有效的丝状病毒疫苗对公共卫生至关重要。在这项研究中,我们比较了通过微针贴片皮内免疫和常规肌肉注射埃博拉病毒(EBOV)糖蛋白(GP)亚单位疫苗在小鼠中诱导的免疫反应,结果表明,微针递送GP诱导的针对GP的抗体反应水平更高且持续时间更长,优于肌肉注射。此外,我们发现,将基于皂苷的佐剂Matrix - M与EBOV GP配制成制剂后,可高效加载到微针贴片上。Matrix - M与GP共同递送显著增强了微针递送诱导的抗体反应,肌肉注射也观察到了同样的情况。攻毒研究结果显示,通过微针或肌肉注射接受GP/佐剂制剂的所有小鼠都能免受致命的EBOV攻毒。此外,通过微针递送无佐剂GP接种的5只小鼠中有4只也在攻毒中存活,而通过肌肉注射无佐剂GP接种的5只小鼠中只有1只在攻毒中存活。这些结果表明,EBOV GP亚单位疫苗的微针贴片递送有望提高安全性和热稳定性,能够提供比肌肉注射更有效的针对EBOV感染的保护。
Development of a safe and efficacious filovirus vaccine is of high importance to public health. In this study, we compared immune responses induced by Ebola virus (EBOV) glycoprotein (GP) subunit vaccines via intradermal immunization with microneedle (MN) patches and the conventional intramuscular (IM) injection in mice, which showed that MN delivery of GP induced higher levels and longer lasting antibody responses against GP than IM injection. Further, we found that EBOV GP in formulation with a saponin-based adjuvant, Matrix-M, can be efficiently loaded onto MN patches. Co-delivery of Matrix-M with GP significantly enhanced induction of antibody responses by MN delivery, as also observed for IM injection. Results from challenge studies showed that all mice that received the GP/adjuvant formulation by MN or IM immunizations were protected from lethal EBOV challenge. Further, 4 out of 5 mice vaccinated by MN delivery of unadjuvanted GP also survived the challenge, whereas only 1 out of 5 mice vaccinated by IM injection of unadjuvanted GP survived the challenge. These results demonstrate that MN patch delivery of EBOV GP subunit vaccines, which is expected to enable improved safety and thermal stability, can confer effective protection against EBOV infection that is superior to IM vaccination.
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