The Amino Acids 736-761 of the MERS-CoV Spike Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

被引:21
作者
Yang, Yang [1 ]
Deng, Yao [1 ]
Wen, Bo [1 ]
Wang, Huijuan [1 ]
Meng, Xin [1 ]
Lan, Jiaming [1 ]
Gao, George F. [2 ]
Tan, Wenjie [1 ]
机构
[1] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Minist Hlth, Key Lab Med Virol, Beijing 102206, Peoples R China
[2] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
关键词
RESPIRATORY SYNDROME CORONAVIRUS; RECEPTOR-BINDING DOMAIN; S PROTEIN; FUNCTIONAL RECEPTOR; SARS CORONAVIRUS; VIRUS; IDENTIFICATION; EPITOPES; TARGET; ENTRY;
D O I
10.1089/vim.2014.0080
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Based on a bioinformatics analysis of the Middle East respiratory syndrome coronavvirus (MERS-CoV) S protein, we synthesized a panel of peptides coupled to keyhole limpet haemocyanin and used them to raise antibodies in rabbits. In addition, the recombinant receptor-binding domain (RBD) was used to raise polyclonal antibodies in mice. All of the antibodies raised by S-peptide immunisation were specific and sensitive for S protein expressed in transfected cells in the indirect immunofluorescence assay or Western blotting. The RBD efficiently elicited neutralizing antibodies against MERS-CoV by blocking viral entry at the binding step. Furthermore, we found that the SP3 peptide, corresponding to amino-acid residues 736-761 of the S protein, elicited robust neutralizing activities by blocking viral entry at the postbinding and membrane fusion steps. We conclude that amino-acid residues 736-761 of the S protein carry neutralizing epitopes that may be used in the development of vaccines and antiviral agents against MERS-CoV.
引用
收藏
页码:543 / 550
页数:8
相关论文
共 30 条
[1]   Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein [J].
Belouzard, Sandrine ;
Millet, Jean K. ;
Licitra, Beth N. ;
Whittaker, Gary R. .
VIRUSES-BASEL, 2012, 4 (06) :1011-1033
[2]   Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk [J].
Breban, Romulus ;
Riou, Julien ;
Fontanet, Arnaud .
LANCET, 2013, 382 (9893) :694-699
[3]   Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms [J].
Coughlin, Melissa M. ;
Babcook, John ;
Prabhakar, Bellur S. .
VIROLOGY, 2009, 394 (01) :39-46
[4]  
De Groot R., 2012, Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses, V1st, P784, DOI DOI 10.1016/B978-0-12-384684-6.00066-5
[5]   Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group [J].
de Groot, Raoul J. ;
Baker, Susan C. ;
Baric, Ralph S. ;
Brown, Caroline S. ;
Drosten, Christian ;
Enjuanes, Luis ;
Fouchier, Ron A. M. ;
Galiano, Monica ;
Gorbalenya, Alexander E. ;
Memish, Ziad A. ;
Perlman, Stanley ;
Poon, Leo L. M. ;
Snijder, Eric J. ;
Stephens, Gwen M. ;
Woo, Patrick C. Y. ;
Zaki, Ali M. ;
Zambon, Maria ;
Ziebuhr, John .
JOURNAL OF VIROLOGY, 2013, 87 (14) :7790-7792
[6]   A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines [J].
Du, Lanying ;
Kou, Zhihua ;
Ma, Cuiqing ;
Tao, Xinrong ;
Wang, Lili ;
Zhao, Guangyu ;
Chen, Yaoqing ;
Yu, Fei ;
Tseng, Chien-Te K. ;
Zhou, Yusen ;
Jiang, Shibo .
PLOS ONE, 2013, 8 (12)
[7]   Identification of a Receptor-Binding Domain in the S Protein of the Novel Human Coronavirus Middle East Respiratory Syndrome Coronavirus as an Essential Target for Vaccine Development [J].
Du, Lanying ;
Zhao, Guangyu ;
Kou, Zhihua ;
Ma, Cuiqing ;
Sun, Shihui ;
Poon, Vincent K. M. ;
Lu, Lu ;
Wang, Lili ;
Debnath, Asim K. ;
Zheng, Bo-Jian ;
Zhou, Yusen ;
Jiang, Shibo .
JOURNAL OF VIROLOGY, 2013, 87 (17) :9939-9942
[8]   The spike protein of SARS-CoV - a target for vaccine and therapeutic development [J].
Du, Lanying ;
He, Yuxian ;
Zhou, Yusen ;
Liu, Shuwen ;
Zheng, Bo-Jian ;
Jiang, Shibo .
NATURE REVIEWS MICROBIOLOGY, 2009, 7 (03) :226-236
[9]   Structure of the Fusion Core and Inhibition of Fusion by a Heptad Repeat Peptide Derived from the S Protein of Middle East Respiratory Syndrome Coronavirus [J].
Gao, Jing ;
Lu, Guangwen ;
Qi, Jianxun ;
Li, Yan ;
Wu, Ying ;
Deng, Yao ;
Geng, Heyuan ;
Li, Hongbin ;
Wang, Qihui ;
Xiao, Haixia ;
Tan, Wenjie ;
Yan, Jinghua ;
Gao, George F. .
JOURNAL OF VIROLOGY, 2013, 87 (24) :13134-13140
[10]   The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies [J].
Gierer, Stefanie ;
Bertram, Stephanie ;
Kaup, Franziska ;
Wrensch, Florian ;
Heurich, Adeline ;
Kraemer-Kuehl, Annika ;
Welsch, Kathrin ;
Winkler, Michael ;
Meyer, Benjamin ;
Drosten, Christian ;
Dittmer, Ulf ;
von Hahn, Thomas ;
Simmons, Graham ;
Hofmann, Heike ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2013, 87 (10) :5502-5511