Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein : Revealing the critical antigenic determinants in inactivated SARS-CoV vaccine
Identifieur interne : 004668 ( Main/Merge ); précédent : 004667; suivant : 004669Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein : Revealing the critical antigenic determinants in inactivated SARS-CoV vaccine
Auteurs : YUXIAN HE [États-Unis] ; JINGJING LI [États-Unis] ; LANYING DU [République populaire de Chine] ; XUXIA YAN [États-Unis] ; GUANEAN HU [République populaire de Chine] ; YUSEN ZHOU [République populaire de Chine] ; SHIBO JIANG [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 2006.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Vaccin.
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Abstract
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.
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Kimball Research Institute, New York Blood Center, 310 East 67th Street</s1><s2>New York, NY 10021</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jingjing Li" sort="Jingjing Li" uniqKey="Jingjing Li" last="Jingjing Li">JINGJING LI</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street</s1><s2>New York, NY 10021</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Lanying Du" sort="Lanying Du" uniqKey="Lanying Du" last="Lanying Du">LANYING DU</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Beijing Institute of Microbiology and Epidemiology</s1><s2>Beijing 100071</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Xuxia Yan" sort="Xuxia Yan" uniqKey="Xuxia Yan" last="Xuxia Yan">XUXIA YAN</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street</s1><s2>New York, NY 10021</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Guanean Hu" sort="Guanean Hu" uniqKey="Guanean Hu" last="Guanean Hu">GUANEAN HU</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Beijing Institute of Microbiology and Epidemiology</s1><s2>Beijing 100071</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yusen Zhou" sort="Yusen Zhou" uniqKey="Yusen Zhou" last="Yusen Zhou">YUSEN ZHOU</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Beijing Institute of Microbiology and Epidemiology</s1><s2>Beijing 100071</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Shibo Jiang" sort="Shibo Jiang" uniqKey="Shibo Jiang" last="Shibo Jiang">SHIBO JIANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street</s1><s2>New York, NY 10021</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigenic determinant</term><term>Identification</term><term>Neutralizing antibody</term><term>Protein</term><term>Severe acute respiratory syndrome</term><term>Vaccine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Identification</term><term>Déterminant antigénique</term><term>Protéine</term><term>Vaccin</term><term>Anticorps neutralisant</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>État de New York</li></region><settlement><li>Pékin</li></settlement></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Yuxian He" sort="Yuxian He" uniqKey="Yuxian He" last="Yuxian He">YUXIAN HE</name></region><name sortKey="Jingjing Li" sort="Jingjing Li" uniqKey="Jingjing Li" last="Jingjing Li">JINGJING LI</name><name sortKey="Shibo Jiang" sort="Shibo Jiang" uniqKey="Shibo Jiang" last="Shibo Jiang">SHIBO JIANG</name><name sortKey="Xuxia Yan" sort="Xuxia Yan" uniqKey="Xuxia Yan" last="Xuxia Yan">XUXIA YAN</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Lanying Du" sort="Lanying Du" uniqKey="Lanying Du" last="Lanying Du">LANYING DU</name></noRegion><name sortKey="Guanean Hu" sort="Guanean Hu" uniqKey="Guanean Hu" last="Guanean Hu">GUANEAN HU</name><name sortKey="Yusen Zhou" sort="Yusen Zhou" uniqKey="Yusen Zhou" last="Yusen Zhou">YUSEN ZHOU</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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