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Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus.

Identifieur interne : 003E15 ( Main/Exploration ); précédent : 003E14; suivant : 003E16

Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus.

Auteurs : Kuo-Ming Lip ; Shuo Shen ; Xiaoming Yang ; Choong-Tat Keng ; Aihua Zhang ; Hsueh-Ling Janice Oh ; Zhi-Hong Li ; Le-Ann Hwang ; Chih-Fong Chou ; Burtram C. Fielding ; Timothy H P. Tan ; Josef Mayrhofer ; Falko G. Falkner ; Jianlin Fu ; Seng Gee Lim ; Wanjin Hong ; Yee-Joo Tan

Source :

RBID : pubmed:16378996

Descripteurs français

English descriptors

Abstract

We have previously shown that an Escherichia coli-expressed, denatured spike (S) protein fragment of the severe acute respiratory coronavirus, containing residues 1029 to 1192 which include the heptad repeat 2 (HR2) domain, was able to induce neutralizing polyclonal antibodies (C. T. Keng, A. Zhang, S. Shen, K. M. Lip, B. C. Fielding, T. H. Tan, C. F. Chou, C. B. Loh, S. Wang, J. Fu, X. Yang, S. G. Lim, W. Hong, and Y. J. Tan, J. Virol. 79:3289-3296, 2005). In this study, monoclonal antibodies (MAbs) were raised against this fragment to identify the linear neutralizing epitopes in the functional domain and to investigate the mechanisms involved in neutralization. Eighteen hybridomas secreting the S protein-specific MAbs were obtained. Binding sites of these MAbs were mapped to four linear epitopes. Two of them were located within the HR2 region and two immediately upstream of the HR2 domain. MAbs targeting these epitopes showed in vitro neutralizing activities and were able to inhibit cell-cell membrane fusion. These results provide evidence of novel neutralizing epitopes that are located in the HR2 domain and the spacer region immediately upstream of the HR2 of the S protein.

DOI: 10.1128/JVI.80.2.941-950.2006
PubMed: 16378996


Affiliations:


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<term>Antibodies, Viral (immunology)</term>
<term>Cell Line</term>
<term>Epitopes (immunology)</term>
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<term>Animaux</term>
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<term>Glycoprotéines membranaires ()</term>
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<term>Humains</term>
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<term>Protéines de l'enveloppe virale</term>
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<front>
<div type="abstract" xml:lang="en">We have previously shown that an Escherichia coli-expressed, denatured spike (S) protein fragment of the severe acute respiratory coronavirus, containing residues 1029 to 1192 which include the heptad repeat 2 (HR2) domain, was able to induce neutralizing polyclonal antibodies (C. T. Keng, A. Zhang, S. Shen, K. M. Lip, B. C. Fielding, T. H. Tan, C. F. Chou, C. B. Loh, S. Wang, J. Fu, X. Yang, S. G. Lim, W. Hong, and Y. J. Tan, J. Virol. 79:3289-3296, 2005). In this study, monoclonal antibodies (MAbs) were raised against this fragment to identify the linear neutralizing epitopes in the functional domain and to investigate the mechanisms involved in neutralization. Eighteen hybridomas secreting the S protein-specific MAbs were obtained. Binding sites of these MAbs were mapped to four linear epitopes. Two of them were located within the HR2 region and two immediately upstream of the HR2 domain. MAbs targeting these epitopes showed in vitro neutralizing activities and were able to inhibit cell-cell membrane fusion. These results provide evidence of novel neutralizing epitopes that are located in the HR2 domain and the spacer region immediately upstream of the HR2 of the S protein.</div>
</front>
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<name sortKey="Mayrhofer, Josef" sort="Mayrhofer, Josef" uniqKey="Mayrhofer J" first="Josef" last="Mayrhofer">Josef Mayrhofer</name>
<name sortKey="Oh, Hsueh Ling Janice" sort="Oh, Hsueh Ling Janice" uniqKey="Oh H" first="Hsueh-Ling Janice" last="Oh">Hsueh-Ling Janice Oh</name>
<name sortKey="Shen, Shuo" sort="Shen, Shuo" uniqKey="Shen S" first="Shuo" last="Shen">Shuo Shen</name>
<name sortKey="Tan, Timothy H P" sort="Tan, Timothy H P" uniqKey="Tan T" first="Timothy H P" last="Tan">Timothy H P. Tan</name>
<name sortKey="Tan, Yee Joo" sort="Tan, Yee Joo" uniqKey="Tan Y" first="Yee-Joo" last="Tan">Yee-Joo Tan</name>
<name sortKey="Yang, Xiaoming" sort="Yang, Xiaoming" uniqKey="Yang X" first="Xiaoming" last="Yang">Xiaoming Yang</name>
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