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

作　　者：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 

机构地区：[1]State Key Laboratory of Pathogen and Biosecurity,AMMS,Beijing,100071,China [2]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),School of Basic Medical Sciences,Shanghai Medical College(SHMC),Fudan University,Shanghai,200032,China [3]Advaccine Biopharmaceutics(Suzhou)Co.LTD,Suzhou,215000,China

出　　处：《Virologica Sinica》2024年第5期812-820,共9页中国病毒学（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFC2302503);the National Natural Science Foundation of China(82241069);Cheng-Feng Qin was supported by the National Science Fund for Distinguished Young Scholars(81925025);the Innovative Research Group from the NSFC(81621005).

摘　　要：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 10μg 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.

关 键 词：Hand foot and mouth disease(HFMD) Human enterovirus 71(EV71) DNA vaccine DNA-launched vaccine Live attenuated vaccine 

分 类 号：R392[医药卫生—免疫学]