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Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine
1 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China 2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 3 Harbin Veterinary Research Institute, Chinese Academy of Agriculture, 427 Maduan Street, Harbin 150001, Ch...
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Published in: | Journal of general virology 2004-10, Vol.85 (10), p.3109-3113 |
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creator | Pang, Hai Liu, Yinggang Han, Xueqing Xu, Yanhui Jiang, Fuguo Wu, Donglai Kong, Xiangang Bartlam, Mark Rao, Zihe |
description | 1 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China
2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3 Harbin Veterinary Research Institute, Chinese Academy of Agriculture, 427 Maduan Street, Harbin 150001, China
Correspondence Zihe Rao raozh{at}xtal.tsinghua.edu.cn
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo , ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection. |
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2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3 Harbin Veterinary Research Institute, Chinese Academy of Agriculture, 427 Maduan Street, Harbin 150001, China
Correspondence Zihe Rao raozh{at}xtal.tsinghua.edu.cn
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo , ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.</description><identifier>ISSN: 0022-1317</identifier><identifier>EISSN: 1465-2099</identifier><identifier>DOI: 10.1099/vir.0.80111-0</identifier><identifier>PMID: 15448374</identifier><identifier>CODEN: JGVIAY</identifier><language>eng</language><publisher>Reading: Soc General Microbiol</publisher><subject>Animals ; Antibodies, Viral - blood ; Biological and medical sciences ; Chlorocebus aethiops ; Coronavirus ; Fundamental and applied biological sciences. Psychology ; Male ; Microbiology ; Miscellaneous ; Neutralization Tests ; Rabbits ; SARS coronavirus ; SARS Virus - immunology ; Severe Acute Respiratory Syndrome - prevention & control ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies ; Vero Cells ; Viral Proteins - immunology ; Viral Vaccines - immunology ; Virology</subject><ispartof>Journal of general virology, 2004-10, Vol.85 (10), p.3109-3113</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-48319ffb7d13426dc6bec34541062ddf8bf27f3f23ae9d8eeacee24a5a4a2daa3</citedby><cites>FETCH-LOGICAL-c423t-48319ffb7d13426dc6bec34541062ddf8bf27f3f23ae9d8eeacee24a5a4a2daa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16157024$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15448374$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pang, Hai</creatorcontrib><creatorcontrib>Liu, Yinggang</creatorcontrib><creatorcontrib>Han, Xueqing</creatorcontrib><creatorcontrib>Xu, Yanhui</creatorcontrib><creatorcontrib>Jiang, Fuguo</creatorcontrib><creatorcontrib>Wu, Donglai</creatorcontrib><creatorcontrib>Kong, Xiangang</creatorcontrib><creatorcontrib>Bartlam, Mark</creatorcontrib><creatorcontrib>Rao, Zihe</creatorcontrib><title>Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine</title><title>Journal of general virology</title><addtitle>J Gen Virol</addtitle><description>1 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China
2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3 Harbin Veterinary Research Institute, Chinese Academy of Agriculture, 427 Maduan Street, Harbin 150001, China
Correspondence Zihe Rao raozh{at}xtal.tsinghua.edu.cn
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo , ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.</description><subject>Animals</subject><subject>Antibodies, Viral - blood</subject><subject>Biological and medical sciences</subject><subject>Chlorocebus aethiops</subject><subject>Coronavirus</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Male</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Neutralization Tests</subject><subject>Rabbits</subject><subject>SARS coronavirus</subject><subject>SARS Virus - immunology</subject><subject>Severe Acute Respiratory Syndrome - prevention & control</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</subject><subject>Vero Cells</subject><subject>Viral Proteins - immunology</subject><subject>Viral Vaccines - immunology</subject><subject>Virology</subject><issn>0022-1317</issn><issn>1465-2099</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqFkT2PEzEQhi0E4nIHJS1yAxLFBn_tFx06wYF0EhRQW7P2ODHaXQfbG5Tfwp_Fe4l0JZWLefS-j2cIecXZlrO-f3_0ccu2HeOcV-wJ2XDV1JUok6dkw5gQFZe8vSLXKf1ijCtVt8_JFa-V6mSrNuTv9xgymuyPSPfLFCKMNGI6hDlhojnQhEeMSMEsGR8mPkIO8UTTabYxTFhBSsF4yGipCTHMUJSW9IH66TB6A9mXLOpCpHmP1GLyu5kGR2Gm6Nyl-rBa-LkaIJWYIxjjZ3xBnjkYE768vDfk5-dPP26_VPff7r7efryvjBIyV-UnvHduaC2XSjTWNAMaqWrFWSOsdd3gROukExKwtx0iGEShoAYFwgLIG_L2nFssfi-Ysp58MjiOMGNYkm6angvZt_8FeduV1r4rYHUGTQwpRXT6EP0E8aQ50-vZdNmRZvrhbJoV_vUleBkmtI_05U4FeHMBIBkYXYTZ-PTINbxumVi5d2du73f7Pz6i3uE8-aIx-LCWdvWqIIuD_AeHvrR9</recordid><startdate>20041001</startdate><enddate>20041001</enddate><creator>Pang, Hai</creator><creator>Liu, Yinggang</creator><creator>Han, Xueqing</creator><creator>Xu, Yanhui</creator><creator>Jiang, Fuguo</creator><creator>Wu, Donglai</creator><creator>Kong, Xiangang</creator><creator>Bartlam, Mark</creator><creator>Rao, Zihe</creator><general>Soc General Microbiol</general><general>Society for General Microbiology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20041001</creationdate><title>Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine</title><author>Pang, Hai ; Liu, Yinggang ; Han, Xueqing ; Xu, Yanhui ; Jiang, Fuguo ; Wu, Donglai ; Kong, Xiangang ; Bartlam, Mark ; Rao, Zihe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-48319ffb7d13426dc6bec34541062ddf8bf27f3f23ae9d8eeacee24a5a4a2daa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Antibodies, Viral - blood</topic><topic>Biological and medical sciences</topic><topic>Chlorocebus aethiops</topic><topic>Coronavirus</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Male</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Neutralization Tests</topic><topic>Rabbits</topic><topic>SARS coronavirus</topic><topic>SARS Virus - immunology</topic><topic>Severe Acute Respiratory Syndrome - prevention & control</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</topic><topic>Vero Cells</topic><topic>Viral Proteins - immunology</topic><topic>Viral Vaccines - immunology</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pang, Hai</creatorcontrib><creatorcontrib>Liu, Yinggang</creatorcontrib><creatorcontrib>Han, Xueqing</creatorcontrib><creatorcontrib>Xu, Yanhui</creatorcontrib><creatorcontrib>Jiang, Fuguo</creatorcontrib><creatorcontrib>Wu, Donglai</creatorcontrib><creatorcontrib>Kong, Xiangang</creatorcontrib><creatorcontrib>Bartlam, Mark</creatorcontrib><creatorcontrib>Rao, Zihe</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of general virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pang, Hai</au><au>Liu, Yinggang</au><au>Han, Xueqing</au><au>Xu, Yanhui</au><au>Jiang, Fuguo</au><au>Wu, Donglai</au><au>Kong, Xiangang</au><au>Bartlam, Mark</au><au>Rao, Zihe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine</atitle><jtitle>Journal of general virology</jtitle><addtitle>J Gen Virol</addtitle><date>2004-10-01</date><risdate>2004</risdate><volume>85</volume><issue>10</issue><spage>3109</spage><epage>3113</epage><pages>3109-3113</pages><issn>0022-1317</issn><eissn>1465-2099</eissn><coden>JGVIAY</coden><abstract>1 Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China
2 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
3 Harbin Veterinary Research Institute, Chinese Academy of Agriculture, 427 Maduan Street, Harbin 150001, China
Correspondence Zihe Rao raozh{at}xtal.tsinghua.edu.cn
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo , ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.</abstract><cop>Reading</cop><pub>Soc General Microbiol</pub><pmid>15448374</pmid><doi>10.1099/vir.0.80111-0</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies, Viral - blood Biological and medical sciences Chlorocebus aethiops Coronavirus Fundamental and applied biological sciences. Psychology Male Microbiology Miscellaneous Neutralization Tests Rabbits SARS coronavirus SARS Virus - immunology Severe Acute Respiratory Syndrome - prevention & control Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Vero Cells Viral Proteins - immunology Viral Vaccines - immunology Virology |
title | Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine |
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