Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.
Identifieur interne : 004951 ( Main/Merge ); précédent : 004950; suivant : 004952Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.
Auteurs : Yuxian He [États-Unis] ; Hong Lu ; Pamela Siddiqui ; Yusen Zhou ; Shibo JiangSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (biosynthèse), Anticorps monoclonaux, Antigènes viraux (), Antigènes viraux (génétique), Cellules Vero, Conformation des protéines, Données de séquences moléculaires, Fragments peptidiques (), Fragments peptidiques (génétique), Fragments peptidiques (immunologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (immunologie), Glycoprotéines membranaires (métabolisme), Humains, Lignée cellulaire, Protéines de fusion recombinantes (), Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (immunologie), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Protéines de l'enveloppe virale (métabolisme), Récepteurs viraux (métabolisme), Sites de fixation, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Techniques in vitro, Tests de neutralisation, Virus du SRAS (génétique), Virus du SRAS (immunologie), Virus du SRAS (pathogénicité), Épitopes (), Épitopes (génétique).
- MESH :
- biosynthèse : Anticorps antiviraux.
- génétique : Antigènes viraux, Fragments peptidiques, Glycoprotéines membranaires, Protéines de fusion recombinantes, Protéines de l'enveloppe virale, Virus du SRAS, Épitopes.
- immunologie : Fragments peptidiques, Glycoprotéines membranaires, Protéines de fusion recombinantes, Protéines de l'enveloppe virale, Virus du SRAS.
- métabolisme : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Récepteurs viraux.
- pathogénicité : Virus du SRAS.
- Animaux, Anticorps monoclonaux, Antigènes viraux, Cellules Vero, Conformation des protéines, Données de séquences moléculaires, Fragments peptidiques, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Lignée cellulaire, Protéines de fusion recombinantes, Protéines de l'enveloppe virale, Sites de fixation, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Techniques in vitro, Tests de neutralisation, Épitopes.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibodies, Viral (biosynthesis), Antigens, Viral (chemistry), Antigens, Viral (genetics), Binding Sites, Cell Line, Chlorocebus aethiops, Epitopes (chemistry), Epitopes (genetics), Humans, In Vitro Techniques, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Membrane Glycoproteins (metabolism), Mice, Mice, Inbred BALB C, Molecular Sequence Data, Neutralization Tests, Peptide Fragments (chemistry), Peptide Fragments (genetics), Peptide Fragments (immunology), Protein Conformation, Receptors, Virus (metabolism), Recombinant Fusion Proteins (chemistry), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (immunology), SARS Virus (genetics), SARS Virus (immunology), SARS Virus (pathogenicity), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Envelope Proteins (metabolism).
- MESH :
- chemical , biosynthesis : Antibodies, Viral.
- chemical , chemistry : Antigens, Viral, Epitopes, Membrane Glycoproteins, Peptide Fragments, Recombinant Fusion Proteins, Viral Envelope Proteins.
- chemical , genetics : Antigens, Viral, Epitopes, Membrane Glycoproteins, Peptide Fragments, Recombinant Fusion Proteins, Viral Envelope Proteins.
- chemical , immunology : Membrane Glycoproteins, Peptide Fragments, Recombinant Fusion Proteins, Viral Envelope Proteins.
- chemical , metabolism : Membrane Glycoproteins, Receptors, Virus, Viral Envelope Proteins.
- chemical : Antibodies, Monoclonal, Spike Glycoprotein, Coronavirus.
- genetics : SARS Virus.
- immunology : SARS Virus.
- pathogenicity : SARS Virus.
- Amino Acid Sequence, Animals, Binding Sites, Cell Line, Chlorocebus aethiops, Humans, In Vitro Techniques, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Neutralization Tests, Protein Conformation, Vero Cells.
Abstract
The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318-510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I-VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 microg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics.
DOI: 10.4049/jimmunol.174.8.4908
PubMed: 15814718
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002802
- to stream PubMed, to step Curation: 002802
- to stream PubMed, to step Checkpoint: 002543
- to stream Ncbi, to step Merge: 000E82
- to stream Ncbi, to step Curation: 000E82
- to stream Ncbi, to step Checkpoint: 000E82
Links to Exploration step
pubmed:15814718Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.</title>
<author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name>
<affiliation wicri:level="2"><nlm:affiliation>Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Hong" sort="Lu, Hong" uniqKey="Lu H" first="Hong" last="Lu">Hong Lu</name>
</author>
<author><name sortKey="Siddiqui, Pamela" sort="Siddiqui, Pamela" uniqKey="Siddiqui P" first="Pamela" last="Siddiqui">Pamela Siddiqui</name>
</author>
<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2005">2005</date>
<idno type="RBID">pubmed:15814718</idno>
<idno type="pmid">15814718</idno>
<idno type="doi">10.4049/jimmunol.174.8.4908</idno>
<idno type="wicri:Area/PubMed/Corpus">002802</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002802</idno>
<idno type="wicri:Area/PubMed/Curation">002802</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002802</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002543</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002543</idno>
<idno type="wicri:Area/Ncbi/Merge">000E82</idno>
<idno type="wicri:Area/Ncbi/Curation">000E82</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000E82</idno>
<idno type="wicri:doubleKey">0022-1767:2005:He Y:receptor:binding:domain</idno>
<idno type="wicri:Area/Main/Merge">004951</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.</title>
<author><name sortKey="He, Yuxian" sort="He, Yuxian" uniqKey="He Y" first="Yuxian" last="He">Yuxian He</name>
<affiliation wicri:level="2"><nlm:affiliation>Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Hong" sort="Lu, Hong" uniqKey="Lu H" first="Hong" last="Lu">Hong Lu</name>
</author>
<author><name sortKey="Siddiqui, Pamela" sort="Siddiqui, Pamela" uniqKey="Siddiqui P" first="Pamela" last="Siddiqui">Pamela Siddiqui</name>
</author>
<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
</author>
</analytic>
<series><title level="j">Journal of immunology (Baltimore, Md. : 1950)</title>
<idno type="ISSN">0022-1767</idno>
<imprint><date when="2005" type="published">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antibodies, Monoclonal</term>
<term>Antibodies, Viral (biosynthesis)</term>
<term>Antigens, Viral (chemistry)</term>
<term>Antigens, Viral (genetics)</term>
<term>Binding Sites</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Epitopes (chemistry)</term>
<term>Epitopes (genetics)</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Membrane Glycoproteins (chemistry)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Neutralization Tests</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (genetics)</term>
<term>Peptide Fragments (immunology)</term>
<term>Protein Conformation</term>
<term>Receptors, Virus (metabolism)</term>
<term>Recombinant Fusion Proteins (chemistry)</term>
<term>Recombinant Fusion Proteins (genetics)</term>
<term>Recombinant Fusion Proteins (immunology)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
<term>SARS Virus (pathogenicity)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vero Cells</term>
<term>Viral Envelope Proteins (chemistry)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux (biosynthèse)</term>
<term>Anticorps monoclonaux</term>
<term>Antigènes viraux ()</term>
<term>Antigènes viraux (génétique)</term>
<term>Cellules Vero</term>
<term>Conformation des protéines</term>
<term>Données de séquences moléculaires</term>
<term>Fragments peptidiques ()</term>
<term>Fragments peptidiques (génétique)</term>
<term>Fragments peptidiques (immunologie)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires ()</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Protéines de fusion recombinantes ()</term>
<term>Protéines de fusion recombinantes (génétique)</term>
<term>Protéines de fusion recombinantes (immunologie)</term>
<term>Protéines de l'enveloppe virale ()</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
<term>Tests de neutralisation</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (immunologie)</term>
<term>Virus du SRAS (pathogénicité)</term>
<term>Épitopes ()</term>
<term>Épitopes (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antigens, Viral</term>
<term>Epitopes</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Fusion Proteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term>
<term>Epitopes</term>
<term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Fusion Proteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Peptide Fragments</term>
<term>Recombinant Fusion Proteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Receptors, Virus</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Anticorps antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes viraux</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
<term>Épitopes</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Fragments peptidiques</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de l'enveloppe virale</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Binding Sites</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Neutralization Tests</term>
<term>Protein Conformation</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Anticorps monoclonaux</term>
<term>Antigènes viraux</term>
<term>Cellules Vero</term>
<term>Conformation des protéines</term>
<term>Données de séquences moléculaires</term>
<term>Fragments peptidiques</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de l'enveloppe virale</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Techniques in vitro</term>
<term>Tests de neutralisation</term>
<term>Épitopes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318-510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I-VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 microg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004951 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 004951 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Main |étape= Merge |type= RBID |clé= pubmed:15814718 |texte= Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:15814718" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |