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Article: 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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TitleRecombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region
 
AuthorsChen, Z3
Zhang, L3
Qin, C2
Ba, L3
Yi, CE3
Zhang, F3
Wei, Q2
He, T3
Yu, W3
Yu, J3
Gao, H2
Tu, X2
Gettie, A3
Farzan, M4
Yuen, KY1
Ho, DD3
 
Issue Date2005
 
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
 
CitationJournal Of Virology, 2005, v. 79 n. 5, p. 2678-2688 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.79.5.2678-2688.2005
 
AbstractImmunization 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.
 
ISSN0022-538X
2013 Impact Factor: 4.648
 
DOIhttp://dx.doi.org/10.1128/JVI.79.5.2678-2688.2005
 
PubMed Central IDPMC548443
 
ISI Accession Number IDWOS:000227098400004
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChen, Z
 
dc.contributor.authorZhang, L
 
dc.contributor.authorQin, C
 
dc.contributor.authorBa, L
 
dc.contributor.authorYi, CE
 
dc.contributor.authorZhang, F
 
dc.contributor.authorWei, Q
 
dc.contributor.authorHe, T
 
dc.contributor.authorYu, W
 
dc.contributor.authorYu, J
 
dc.contributor.authorGao, H
 
dc.contributor.authorTu, X
 
dc.contributor.authorGettie, A
 
dc.contributor.authorFarzan, M
 
dc.contributor.authorYuen, KY
 
dc.contributor.authorHo, DD
 
dc.date.accessioned2008-06-12T06:35:44Z
 
dc.date.available2008-06-12T06:35:44Z
 
dc.date.issued2005
 
dc.description.abstractImmunization 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.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent386 bytes
 
dc.format.mimetypetext/html
 
dc.identifier.citationJournal Of Virology, 2005, v. 79 n. 5, p. 2678-2688 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.79.5.2678-2688.2005
 
dc.identifier.doihttp://dx.doi.org/10.1128/JVI.79.5.2678-2688.2005
 
dc.identifier.epage2688
 
dc.identifier.hkuros109678
 
dc.identifier.isiWOS:000227098400004
 
dc.identifier.issn0022-538X
2013 Impact Factor: 4.648
 
dc.identifier.issue5
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC548443
 
dc.identifier.pmid15708987
 
dc.identifier.scopuseid_2-s2.0-13944272585
 
dc.identifier.spage2678
 
dc.identifier.urihttp://hdl.handle.net/10722/49158
 
dc.identifier.volume79
 
dc.languageeng
 
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Virology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.rightsCopyright © American Society for Microbiology, Journal of Virology, 2005, v. 79 n. 5, p. 2678-2688
 
dc.subject.meshAntibodies, Viral - biosynthesis
 
dc.subject.meshMembrane Glycoproteins - chemistry - genetics - immunology
 
dc.subject.meshSARS Virus - genetics - immunology
 
dc.subject.meshVaccinia virus - genetics
 
dc.subject.meshViral Envelope Proteins - chemistry - genetics - immunology
 
dc.titleRecombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Chinese Academy of Medical Sciences
  3. Rockefeller University
  4. Brigham and Women's Hospital