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

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

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

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

cstr: 32224.14.j.virs.2024.09.008

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
Available online: 19 September 2024

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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