Division of Vaccine Research, National Research Institute of Health, Centers for Disease Control and Prevention, Osong-eup, CheongJu, Chungcheongbuk-do, Republic of Korea.
College of Medicine and Medical Research Institute, Chungbuk National University, CheongJu, Chungcheongbuk-do, Republic of Korea.
PLoS One. 2018 Oct 2;13(10):e0202552. doi: 10.1371/journal.pone.0202552. eCollection 2018.
Enterovirus 71 (EV71) is a major etiological agent of various public health issues, particularly in the Asia-Pacific region. EV71 causes hand-foot-and-mouth disease (HFMD) and is associated with serious neurological disorders in young children. A formalin-inactivated EV71 candidate vaccine (KCDC-HFMDV1-EV71) based on the C4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of EV71 infection in mice. In this study, an inactivated EV71 vaccine was used for analysis of long-term immunogenicity and efficacy in cynomolgus monkeys, a common nonhuman primate model. The vaccine was immunized three times at 0, 4, and 8 weeks with either 20-μg doses of EV71 candidate vaccine formulated with aluminum hydroxide gel adjuvant or phosphate-buffered saline as a control. The group immunized with the inactivated EV71 showed significantly increased EV71-specific antibody and serum neutralizing antibody titers at 3 weeks after vaccination and maintained these elevated titers until the end of the experiment (54 weeks after vaccination). The sera from vaccinated cynomolgus monkeys showed a crossreactive neutralizing antibody response to the heterologous subtype of EV71 (B1-4, C1, and C2). These findings suggest that the inactivated EV71 candidate vaccine may be a potential vaccine candidate and valuable tool for the control of HFMD.
肠道病毒 71 型(EV71)是多种公共卫生问题的主要病原体,特别是在亚太地区。EV71 引起手足口病(HFMD),并与幼儿严重的神经系统疾病有关。此前,基于 C4 亚属型,已开发出一种基于福尔马林灭活的 EV71 候选疫苗(KCDC-HFMDV1-EV71),并在小鼠中证实其具有预防 EV71 感染的潜力。在这项研究中,使用灭活的 EV71 疫苗分析了其在食蟹猴(一种常见的非人类灵长类动物模型)中的长期免疫原性和疗效。该疫苗在 0、4 和 8 周时使用氢氧化铝凝胶佐剂配制的 20μg 剂量的 EV71 候选疫苗或磷酸盐缓冲盐水(作为对照)进行三次免疫接种。与对照组相比,接种灭活 EV71 的组在接种后 3 周时 EV71 特异性抗体和血清中和抗体滴度显著增加,并保持这些升高的滴度直至实验结束(接种后 54 周)。来自接种疫苗的食蟹猴的血清显示出对异源亚型 EV71(B1-4、C1 和 C2)的交叉反应性中和抗体反应。这些发现表明,灭活的 EV71 候选疫苗可能是一种有潜力的候选疫苗,也是控制手足口病的有价值工具。