Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

Rong-Rong Zhang; Meng-Jiao He; Chao Zhou; Yan-Peng Xu; Wei Tang; Tian-Shu Cao; Zheng-Jian Wang; Mei Wu; Tao Ming; Yi-Jiao Huang; Meng-Xu Sun; Hui Zhao; Yong-Qiang Deng; Xiao-Feng Li; Bin Wang; Qing Ye; Cheng-Feng Qin

doi:10.1016/j.virs.2024.09.008

October 2024

. doi: 10.1016/j.virs.2024.09.008

Citation: Rong-Rong Zhang, Meng-Jiao He, Chao Zhou, Yan-Peng Xu, Wei Tang, Tian-Shu Cao, Zheng-Jian Wang, Mei Wu, Tao Ming, Yi-Jiao Huang, Meng-Xu Sun, Hui Zhao, Yong-Qiang Deng, Xiao-Feng Li, Bin Wang, Qing Ye, Cheng-Feng Qin. Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71 .VIROLOGICA SINICA, 2024, 39(5) : 812-820. http://dx.doi.org/10.1016/j.virs.2024.09.008

肠道病毒71型DNA启动型减毒活疫苗的设计

张蓉蓉 ^a ,
贺梦娇 ^a ,
周超 ^a ,
徐炎鹏 ^a ,
唐维 ^a ,
曹天舒 ^a ,
王峥鉴 ^a ,
武媚 ^a ,
明涛 ^a ,
黄怡娇 ^a ,
孙梦许 ^a ,
赵慧 ^a ,
邓永强 ^a ,
李晓峰 ^a ,
王宾 ^b,c ,
叶青 ^a,, ,
秦成峰 ^a,,

cstr: 32224.14.j.virs.2024.09.008

a. 病原微生物生物安全全国重点实验室, 军事医学研究院;
b. 医学分子病毒学重点实验室(教育部/卫健委/中国医科院), 上海医学院基础医学院, 复旦大学;
c. 艾棣维欣(苏州)生物制药有限公司

通讯作者： 叶青, yy.0526@163.com; 秦成峰, qincf@bmi.ac.cn

摘要

人类肠道病毒71型（EV71）是手足口病（HFMD）的主要病原体之一，对全球健康具有重大影响。尽管已有EV71灭活疫苗获批上市，但基于先进技术平台的候选疫苗研发仍具有重要意义。本文设计并构建了两种由真核启动子启动转录的DNA启动型减毒候选活疫苗（pDL-EV71）。通过在体外和体内转染pDL-EV71，能够成功拯救并获得完整的 EV71 病毒颗粒。更重要的是，pDL-EV71通过颅内注射新生乳鼠或肌肉注射 I 型干扰素受体缺陷小鼠均未引起典型的临床症状，初步证明了其具有良好的安全性。此外，pDL-EV71 单针或两针免疫可以在小鼠中诱导针对 EV71 的高水平中和抗体和抗原特异性细胞免疫反应。10 μg pDL-EV71单针免疫可以完全保护免疫母鼠所产新生小鼠免受致死剂量的 EV71感染。综上，本研究成功设计了一种安全有效的EV71候选疫苗，为其进一步开发和应用提供了重要实验基础。
- 手足口病
- , 肠道病毒71型
- , DNA疫苗
- , DNA启动型疫苗
- , 减毒活疫苗

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

a. State Key Laboratory of Pathogen and Biosecurity, AMMS, Beijing, 100071, China;
b. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College (SHMC), Fudan University, Shanghai, 200032, China;
c. Advaccine Biopharmaceutics (Suzhou) Co. LTD, Suzhou, 215000, China

Corresponding author: Qing Ye, yy.0526@163.com Cheng-Feng Qin, qincf@bmi.ac.cn

Abstract

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR^-/- mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.
- Hand, foot and mouth disease (HFMD)
- , Human enterovirus 71(EV71)
- , DNA vaccine
- , DNA-launched vaccine
- , Live attenuated vaccine

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