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在食蟹猴中诱导的灭活肠道病毒 71 引起的增强中和抗体反应。

Enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys.

机构信息

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.

出版信息

PLoS One. 2018 Oct 2;13(10):e0202552. doi: 10.1371/journal.pone.0202552. eCollection 2018.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5a/6168120/ba45c8c1bdce/pone.0202552.g001.jpg

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