title: Transcutaneous immunization via rapidly dissolvable microneedles protects against hand-foot-and-mouth disease caused by enterovirus 71.
abstract: 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 3h even at a high relative humidity of 75%. With the aid of spring-operated applicator, EV71 MNs (approximately 500μm length) could be readily penetrated into the mouse skin in vivo, and then rapidly dissolved to release encapsulated antigen within 2min. 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.
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
authors: Zhuangzhi
authors: Z
authors: Zhu
authors: Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Xiaohua
authors: X
authors: Ye
authors: Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Zhiqiang
authors: Z
authors: Ku
authors: Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Qingwei
authors: Q
authors: Liu
authors: Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Chaoyun
authors: C
authors: Shen
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
authors: Huafei
authors: H
authors: Luo
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
authors: Hansen
authors: H
authors: Luan
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
authors: Chenghao
authors: C
authors: Zhang
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China.
authors: Shaoqiong
authors: S
authors: Tian
authors: Micropoint Technologies Pte. Ltd., Singapore 637141, Singapore.
authors: CheeYen
authors: C
authors: Lim
authors: Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: huangzhong@ips.ac.cn.
authors: Zhong
authors: Z
authors: Huang
authors: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, China. Electronic address: wanghao10@sinopharm.com.
authors: Hao
authors: H
authors: Wang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000917:Antibody Formation; D004355:Drug Stability; D004356:Drug Storage; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000517:prevention & control*; D006820:Hyaluronic Acid / Q000737:chemistry; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D012869:Skin Absorption; D013997:Time Factors; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D014765:Viral Vaccines; D006820:Hyaluronic Acid
keywords: Dissolving microneedles; Dose sparing; Enterovirus 71; Hand-foot-and-mouth disease; Transcutaneous immunization; Virus-like particles