Transcutaneous immunization via rapidly dissolvable microneedles protects against hand-foot-and-mouth disease caused by enterovirus 71

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• 作者：Zhuangzhi Zhu^a ; ¹ ; Xiaohua Ye^b ; ¹ ; Zhiqiang Ku^b ; Qingwei Liu^b ; Chaoyun Shen^b ; Huafei Luo^a ; Hansen Luan^a ; Chenghao Zhang^a ; Shaoqiong Tian^a ; CheeYen Lim^c ; Zhong Huang^b ; ^{huangzhong@ips.ac.cn} ; Hao Wang^a ; ^{wanghao10@sinopharm.com}
• 关键词：Dissolving microneedles ; Transcutaneous immunization ; Hand-foot-and-mouth disease ; Enterovirus 71 ; Virus-like particles ; Dose sparing
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 December 2016
• 年：2016
• 卷：243
• 期：Complete
• 页码：291-302
• 全文大小：1924 K
• 卷排序：243

文摘

Recent large outbreaks of hand-foot-and-mouth disease (HFMD) have seriously affected the health of young children. Enterovirus 71 (EV71) is the main causative agent of HFMD. Herein, for the first time, rapidly dissolvable microneedles (MNs) loaded with EV71 virus-like particles (VLPs) were evaluated whether they could induce robust immune responses that confer protection against EV71 infection. The characteristics of prepared MNs including hygroscopy, mechanical strength, insertion capacity, dissolution profile, skin irritation and storage stability were comprehensively assessed. EV71 VLPs remained morphologically stable during fabrication. The MNs made of sodium hyaluronate maintained their insertion ability for at least 3 h even at a high relative humidity of 75%. With the aid of spring-operated applicator, EV71 MNs (approximately 500 μm length) could be readily penetrated into the mouse skin in vivo, and then rapidly dissolved to release encapsulated antigen within 2 min. Additionally, MNs induced slight erythema that disappeared within a few hours. More importantly, mouse immunization and virus challenge studies demonstrated that MNs immunization induced high level of antibody responses conferring full protection against lethal EV71 virus challenge that were comparable to conventional intramuscular injection, but with only 1/10th of the delivered antigen (dose sparing). Consequently, our rapidly dissolving MNs may present as an effective and promising transcutaneous immunization device for HFMD prophylaxis among children.