SrasV1, Main, Exploration, bibRecord, 004682

Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region

Identifieur interne : 004682 ( Main/Exploration ); précédent : 004681; suivant : 004683

Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region

Auteurs : Zhiwei Chen ; Linqi Zhang ; Chuan Qin ; Lei Ba ; Christopher E. Yi ; Fengwen Zhang ; Qiang Wei ; Tian He ; Wenjie Yu ; Jian Yu ; Hong Gao ; Xinming Tu ; Agegnehu Gettie ; Michael Farzan ; Kwok-Yung Yuen ; David D. Ho

Source :

Journal of Virology [ 0022-538X ] ; 2005.

RBID : PMC:548443

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Viral (biosynthesis), Antigens, Viral (chemistry), Antigens, Viral (genetics), Carboxypeptidases (physiology), Epitope Mapping, Genes, Viral, Genetic Vectors, Macaca mulatta, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Membrane Glycoproteins (immunology), Neutralization Tests, Peptidyl-Dipeptidase A, Protein Structure, Tertiary, Rabbits, Receptors, Virus (physiology), Recombination, Genetic, SARS Virus (genetics), SARS Virus (immunology), Spike Glycoprotein, Coronavirus, Vaccinia virus (genetics), Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (genetics), Viral Vaccines (immunology).
MESH :
- chemical , administration & dosage : Viral Vaccines.
- chemical , biosynthesis : Antibodies, Viral.
- chemical , chemistry : Antigens, Viral, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Antigens, Viral, Membrane Glycoproteins, Viral Envelope Proteins, Viral Vaccines.
- chemical , immunology : Membrane Glycoproteins, Viral Envelope Proteins, Viral Vaccines.
- chemical , physiology : Carboxypeptidases, Receptors, Virus.
- genetics : SARS Virus, Vaccinia virus.
- immunology : SARS Virus.
- Animals, Epitope Mapping, Genes, Viral, Genetic Vectors, Macaca mulatta, Neutralization Tests, Peptidyl-Dipeptidase A, Protein Structure, Tertiary, Rabbits, Recombination, Genetic, Spike Glycoprotein, Coronavirus.

Abstract

Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. In this study, we generated a SARS vaccine candidate by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. The newly generated recombinant MVA, ADS-MVA, is replication incompetent in mammalian cells and highly immunogenic in terms of inducing potent neutralizing antibodies in mice, rabbits, and monkeys. After two intramuscular vaccinations with ADS-MVA alone, the 50% inhibitory concentration in serum was achieved with reciprocal sera dilutions of more than 1,000- to 10,000-fold in these animals. Using fragmented S genes as immunogens, we also mapped a neutralizing epitope in the region of N-terminal 400 to 600 amino acids of the S glycoprotein (S400-600), which overlaps with the angiotensin-converting enzyme 2 (ACE2) receptor-binding region (RBR; S318-510). Moreover, using a recombinant soluble RBR-Fc protein, we were able to absorb and remove the majority of the neutralizing antibodies despite observing that the full S protein tends to induce a broader spectrum of neutralizing activities in comparison with fragmented S proteins. Our data suggest that a major mechanism for neutralizing SARS-CoV likely occurs through blocking the interaction between virus and the cellular receptor ACE2. In addition, ADS-MVA induced potent immune responses which very likely protected Chinese rhesus monkeys from pathogenic SARS-CoV challenge.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC548443

DOI: 10.1128/JVI.79.5.2678-2688.2005
PubMed: 15708987
PubMed Central: 548443

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region</title>
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<term>Antigens, Viral (chemistry)</term>
<term>Antigens, Viral (genetics)</term>
<term>Carboxypeptidases (physiology)</term>
<term>Epitope Mapping</term>
<term>Genes, Viral</term>
<term>Genetic Vectors</term>
<term>Macaca mulatta</term>
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<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Neutralization Tests</term>
<term>Peptidyl-Dipeptidase A</term>
<term>Protein Structure, Tertiary</term>
<term>Rabbits</term>
<term>Receptors, Virus (physiology)</term>
<term>Recombination, Genetic</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
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<term>Vaccinia virus (genetics)</term>
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<term>Viral Envelope Proteins (genetics)</term>
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<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
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<term>Antigènes viraux (génétique)</term>
<term>Carboxypeptidases (physiologie)</term>
<term>Cartographie épitopique</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires ()</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Gènes viraux</term>
<term>Lapins</term>
<term>Macaca mulatta</term>
<term>Peptidyl-Dipeptidase A</term>
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<term>Vaccins antiviraux (immunologie)</term>
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<term>Virus du SRAS (génétique)</term>
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<term>Virus du SRAS</term>
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<front><div type="abstract" xml:lang="en"><p>Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. In this study, we generated a SARS vaccine candidate by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector. The full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. The newly generated recombinant MVA, ADS-MVA, is replication incompetent in mammalian cells and highly immunogenic in terms of inducing potent neutralizing antibodies in mice, rabbits, and monkeys. After two intramuscular vaccinations with ADS-MVA alone, the 50% inhibitory concentration in serum was achieved with reciprocal sera dilutions of more than 1,000- to 10,000-fold in these animals. Using fragmented S genes as immunogens, we also mapped a neutralizing epitope in the region of N-terminal 400 to 600 amino acids of the S glycoprotein (S400-600), which overlaps with the angiotensin-converting enzyme 2 (ACE2) receptor-binding region (RBR; S318-510). Moreover, using a recombinant soluble RBR-Fc protein, we were able to absorb and remove the majority of the neutralizing antibodies despite observing that the full S protein tends to induce a broader spectrum of neutralizing activities in comparison with fragmented S proteins. Our data suggest that a major mechanism for neutralizing SARS-CoV likely occurs through blocking the interaction between virus and the cellular receptor ACE2. In addition, ADS-MVA induced potent immune responses which very likely protected Chinese rhesus monkeys from pathogenic SARS-CoV challenge.</p>
</div>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Ba, Lei" sort="Ba, Lei" uniqKey="Ba L" first="Lei" last="Ba">Lei Ba</name>
<name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name>
<name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name>
<name sortKey="Gao, Hong" sort="Gao, Hong" uniqKey="Gao H" first="Hong" last="Gao">Hong Gao</name>
<name sortKey="Gettie, Agegnehu" sort="Gettie, Agegnehu" uniqKey="Gettie A" first="Agegnehu" last="Gettie">Agegnehu Gettie</name>
<name sortKey="He, Tian" sort="He, Tian" uniqKey="He T" first="Tian" last="He">Tian He</name>
<name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name>
<name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name>
<name sortKey="Tu, Xinming" sort="Tu, Xinming" uniqKey="Tu X" first="Xinming" last="Tu">Xinming Tu</name>
<name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name>
<name sortKey="Yi, Christopher E" sort="Yi, Christopher E" uniqKey="Yi C" first="Christopher E." last="Yi">Christopher E. Yi</name>
<name sortKey="Yu, Jian" sort="Yu, Jian" uniqKey="Yu J" first="Jian" last="Yu">Jian Yu</name>
<name sortKey="Yu, Wenjie" sort="Yu, Wenjie" uniqKey="Yu W" first="Wenjie" last="Yu">Wenjie Yu</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zhang, Fengwen" sort="Zhang, Fengwen" uniqKey="Zhang F" first="Fengwen" last="Zhang">Fengwen Zhang</name>
<name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name>
</noCountry>
</tree>
</affiliations>
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       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

Serveur d'exploration SRAS

Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region

Recombinant Modified Vaccinia Virus Ankara Expressing the Spike Glycoprotein of Severe Acute Respiratory Syndrome Coronavirus Induces Protective Neutralizing Antibodies Primarily Targeting the Receptor Binding Region

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Pour générer des pages wiki

	Serveur d'exploration SRAS
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