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一种使用从韩国患者分离出的肠道病毒71型(C4a)毒株制成的手足口病灭活疫苗在小鼠中引发强烈的免疫原性反应。

An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice.

作者信息

In Hyun Ju, Lim Heeji, Lee Jung-Ah, Kim Hye Jin, Kim Jin-Won, Hyeon Ji-Yeon, Yeo Sang-Gu, Lee June-Woo, Yoo Jung Sik, Choi Young Ki, Lee Sang-Won

机构信息

Division of Vaccine Research, Korea National Research Institute of Health, Korea Centers for Disease Control and Prevention, 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. 2017 May 24;12(5):e0178259. doi: 10.1371/journal.pone.0178259. eCollection 2017.

Abstract

Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

摘要

肠道病毒71型(EV71)是儿童手足口病(HFMD)的主要病原体。由EV71引起的手足口病可导致严重的健康问题,且已在全球范围内报道,尤其是在亚太地区。在本研究中,我们使用从一名韩国患者分离出的EV71毒株(甲醛灭活手足口病疫苗FI-EV71 C4a)评估了甲醛灭活手足口病疫苗的免疫原性。在小鼠中对候选疫苗进行评估以确定接种剂量和疫苗接种方案。给BALB/c小鼠肌肉注射5、10或20μg的FI-EV71疫苗,2周后进行加强免疫。在所有接种组中均诱导并维持了EV71特异性抗体和中和抗体直至实验期结束。为了确定EV71疫苗佐剂的有效性,将三种佐剂,即氢氧化铝凝胶、单磷酰脂质A和聚肌苷酸-聚胞苷酸,分别与FI-EV71疫苗通过肌肉途径注射给小鼠。与单一佐剂组相比,用所有三种佐剂配制的FI-EV71疫苗给药的小鼠诱导出显著增强的抗体反应。三联佐剂接种组比其他组表现出更快诱导EV71特异性抗体和中和抗体。这些结果表明佐剂在灭活疫苗中对于引发针对EV71的有效免疫反应很重要。总之,我们的结果表明FI-EV71是预防EV71感染的潜在候选疫苗。

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