Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein

作     者：Hongyue Li Yuhang Zhang Dong Li Yong-Qiang Deng Hongde Xu Chaoyue Zhao Jiandong Liu Dan Wen Jianguo Zhao Yongchun Li Yong Wu Shujun Liu Jiankai Liu Junfeng Hao Fei Yuan Shuguang Duo Cheng-Feng Qin Aihua Zheng Hongyue Li;Yuhang Zhang;Dong Li;Yong-Qiang Deng;Hongde Xu;Chaoyue Zhao;Jiandong Liu;Dan Wen;Jianguo Zhao;Yongchun Li;Yong Wu;Shujun Liu;Jiankai Liu;Junfeng Hao;Fei Yuan;Shuguang Duo;Cheng-Feng Qin;Aihua Zheng

作者机构：State Key Laboratory of Integrated Management of Pest Insects and RodentsInstitute of ZoologyChinese Academy of Sciences100101 BeijingChina CAS Center for Excellence in Biotic InteractionsUniversity of Chinese Academy of Sciences100101 BeijingChina Shenzhen KangtaiBiotechnology Co.Ltd518106 ShenzhenGuangdongChina State Key Laboratory of Pathogen and BiosecurityInstitute of Microbiology and EpidemiologyAcademy of Military Medical Sciences100071 BeijingChina School of Pharmaceutical SciencesZhengzhou University450001 ZhengzhouHenanChina State Key Laboratory of Stem cell and Reproductive BiologyInstitute of ZoologyChinese Academy of Sciences100101 BeijingChina Division of Animal Model ResearchInstitute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629 BeijingChina Laboratory Animal CenterInstitute of ZoologyChinese Academy of Sciences100101 BeijingChina Core Facility for Protein ResearchInstitute of BiophysicsChinese Academy of Sciences100101 BeijingChina College of Life ScienceHenan Normal University453007 XinxiangChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2021年第6卷第12期

页      面：3697-3708页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：This project was funded by the National Key Plan for Scientific Research and Development of China(2016YFD0500303,2018YFA0900801) the National Science and Technology Major Project(2018ZX10101004) National Natural Science Foundation of China,General Program(81871687) the Key Research Program of the Chinese Academy of Sciences(KJZD-SW-L06) 

主　　题：ACE2 immunity protective 

摘      要：SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor *** replacing the VSV glycoprotein with the spikes(S)of SARS-CoV-2 and SARS-CoV,we generated two replication-competent recombinant viruses,rVSVSARS-CoV-2 and *** wild-type and human ACE2(hACE2)knock-in mouse models,we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal(i.n.)and intramuscular(i.m.)*** the high genetic similarity between SARS-CoV-2 and SARS-CoV,no obvious cross-neutralizing activity was observed in the immunized mice *** macaques,neutralizing antibody(NAb)titers induced by one *** of rVSV-SARS-CoV-2 were eight-fold higher than those by a single ***,our data indicates that rVSV-SARS-CoV-2 might be suitable for *** instead of the traditional *** in *** rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV2 in a route-independent manner,we generated a chimeric antigen by replacing the receptor binding domain(RBD)of SARS-CoV S with that from the *** expressing the chimera(rVSV-SARS-CoV/2-RBD)induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2,with a safe Th1-biased *** immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with ***2 mice receiving a single *** of either rVSV-SARS-CoV-2 or rVSV-SARSCoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the *** results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.