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 : 004D74 ( Main/Exploration ); précédent : 004D73; suivant : 004D75Recombinant 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 [États-Unis] ; LINQI ZHANG [États-Unis] ; CHUAN QIN [République populaire de Chine] ; LEI BA [États-Unis] ; Christopher E. Yi [États-Unis] ; FENGWEN ZHANG [États-Unis] ; QIANG WEI [République populaire de Chine] ; TIAN HE [États-Unis] ; WENJIE YU [États-Unis] ; JIAN YU [États-Unis] ; HONG GAO [République populaire de Chine] ; XINMING TU [République populaire de Chine] ; Agegnehu Gettie [États-Unis] ; Michael Farzan [États-Unis] ; Kwok-Yung Yuen [Hong Kong] ; David D. Ho [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2005.
Descripteurs français
- Pascal (Inist)
English descriptors
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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.
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Yi</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Fengwen Zhang" sort="Fengwen Zhang" uniqKey="Fengwen Zhang" last="Fengwen Zhang">FENGWEN ZHANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Qiang Wei" sort="Qiang Wei" uniqKey="Qiang Wei" last="Qiang Wei">QIANG WEI</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Science</s1><s2>Beijing</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tian He" sort="Tian He" uniqKey="Tian He" last="Tian He">TIAN HE</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Wenjie Yu" sort="Wenjie Yu" uniqKey="Wenjie Yu" last="Wenjie Yu">WENJIE YU</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jian Yu" sort="Jian Yu" uniqKey="Jian Yu" last="Jian Yu">JIAN YU</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 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Yi</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Fengwen Zhang" sort="Fengwen Zhang" uniqKey="Fengwen Zhang" last="Fengwen Zhang">FENGWEN ZHANG</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Qiang Wei" sort="Qiang Wei" uniqKey="Qiang Wei" last="Qiang Wei">QIANG WEI</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Science</s1><s2>Beijing</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tian He" sort="Tian He" uniqKey="Tian He" last="Tian He">TIAN HE</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Wenjie Yu" sort="Wenjie Yu" uniqKey="Wenjie Yu" last="Wenjie Yu">WENJIE YU</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jian Yu" sort="Jian Yu" uniqKey="Jian Yu" last="Jian Yu">JIAN YU</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Hong Gao" sort="Hong Gao" uniqKey="Hong Gao" last="Hong Gao">HONG GAO</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Science</s1><s2>Beijing</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Xinming Tu" sort="Xinming Tu" uniqKey="Xinming Tu" last="Xinming Tu">XINMING TU</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Laboratory Animal Science, Chinese Academy of Medical Science</s1><s2>Beijing</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gettie, Agegnehu" sort="Gettie, Agegnehu" uniqKey="Gettie A" first="Agegnehu" last="Gettie">Agegnehu Gettie</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Partners AIDS Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston, Massachusetts</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Microbiology, University of Hong Kong</s1><s3>HKG</s3><sZ>15 aut.</sZ></inist:fA14><country>Hong Kong</country><wicri:noRegion>Department of Microbiology, University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Aaron Diamond AIDS Research Center, The Rockefeller University</s1><s2>New York, New York</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>13 aut.</sZ><sZ>16 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">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term><term>Glycoprotein</term><term>Microbiology</term><term>Neutralizing antibody</term><term>Recombinant virus</term><term>Severe acute respiratory syndrome</term><term>Targeting</term><term>Vaccinia virus</term><term>Virology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Virus vaccine</term><term>Coronavirus</term><term>Virus recombinant</term><term>Glycoprotéine</term><term>Anticorps neutralisant</term><term>Ciblage</term><term>Microbiologie</term><term>Virologie</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Massachusetts</li><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="Zhiwei Chen" sort="Zhiwei Chen" uniqKey="Zhiwei Chen" last="Zhiwei Chen">ZHIWEI CHEN</name></region><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name><name sortKey="Fengwen Zhang" sort="Fengwen Zhang" uniqKey="Fengwen Zhang" last="Fengwen Zhang">FENGWEN ZHANG</name><name sortKey="Gettie, Agegnehu" sort="Gettie, Agegnehu" uniqKey="Gettie A" first="Agegnehu" last="Gettie">Agegnehu Gettie</name><name sortKey="Ho, David D" sort="Ho, David D" uniqKey="Ho D" first="David D." last="Ho">David D. Ho</name><name sortKey="Jian Yu" sort="Jian Yu" uniqKey="Jian Yu" last="Jian Yu">JIAN YU</name><name sortKey="Lei Ba" sort="Lei Ba" uniqKey="Lei Ba" last="Lei Ba">LEI BA</name><name sortKey="Linqi Zhang" sort="Linqi Zhang" uniqKey="Linqi Zhang" last="Linqi Zhang">LINQI ZHANG</name><name sortKey="Tian He" sort="Tian He" uniqKey="Tian He" last="Tian He">TIAN HE</name><name sortKey="Wenjie Yu" sort="Wenjie Yu" uniqKey="Wenjie Yu" last="Wenjie Yu">WENJIE YU</name><name sortKey="Yi, Christopher E" sort="Yi, Christopher E" uniqKey="Yi C" first="Christopher E." last="Yi">Christopher E. Yi</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Chuan Qin" sort="Chuan Qin" uniqKey="Chuan Qin" last="Chuan Qin">CHUAN QIN</name></noRegion><name sortKey="Hong Gao" sort="Hong Gao" uniqKey="Hong Gao" last="Hong Gao">HONG GAO</name><name sortKey="Qiang Wei" sort="Qiang Wei" uniqKey="Qiang Wei" last="Qiang Wei">QIANG WEI</name><name sortKey="Xinming Tu" sort="Xinming Tu" uniqKey="Xinming Tu" last="Xinming Tu">XINMING TU</name></country><country name="Hong Kong"><noRegion><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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