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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

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
Authors
Issue Date2005
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2005, v. 79 n. 5, p. 2678-2688 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/49158
ISSN
2013 Impact Factor: 4.648
PubMed Central ID
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong
  2. Chinese Academy of Medical Sciences
  3. Rockefeller University
  4. Brigham and Women's Hospital
DC FieldValueLanguage
dc.contributor.authorChen, Zen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorQin, Cen_HK
dc.contributor.authorBa, Len_HK
dc.contributor.authorYi, CEen_HK
dc.contributor.authorZhang, Fen_HK
dc.contributor.authorWei, Qen_HK
dc.contributor.authorHe, Ten_HK
dc.contributor.authorYu, Wen_HK
dc.contributor.authorYu, Jen_HK
dc.contributor.authorGao, Hen_HK
dc.contributor.authorTu, Xen_HK
dc.contributor.authorGettie, Aen_HK
dc.contributor.authorFarzan, Men_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorHo, DDen_HK
dc.date.accessioned2008-06-12T06:35:44Z-
dc.date.available2008-06-12T06:35:44Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Virology, 2005, v. 79 n. 5, p. 2678-2688en_HK
dc.identifier.issn0022-538Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/49158-
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.en_HK
dc.format.extent386 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_HK
dc.relation.ispartofJournal of Virologyen_HK
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsCopyright © American Society for Microbiology, Journal of Virology, 2005, v. 79 n. 5, p. 2678-2688en_HK
dc.subject.meshAntibodies, Viral - biosynthesisen_HK
dc.subject.meshMembrane Glycoproteins - chemistry - genetics - immunologyen_HK
dc.subject.meshSARS Virus - genetics - immunologyen_HK
dc.subject.meshVaccinia virus - geneticsen_HK
dc.subject.meshViral Envelope Proteins - chemistry - genetics - immunologyen_HK
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 regionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-538X&volume=79&issue=5&spage=2678&epage=2688&date=2005&atitle=Recombinant+modified+vaccinia+virus+Ankara+expressing+the+spike+glycoprotein+of+severe+acute+respiratory+syndrome+coronavirus+induces+protective+neutralizing+antibodies+primarily+targeting+the+receptor+binding+regionen_HK
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityChen, Z=rp00243en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1128/JVI.79.5.2678-2688.2005en_HK
dc.identifier.pmid15708987en_HK
dc.identifier.pmcidPMC548443en_HK
dc.identifier.scopuseid_2-s2.0-13944272585en_HK
dc.identifier.hkuros109678-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13944272585&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume79en_HK
dc.identifier.issue5en_HK
dc.identifier.spage2678en_HK
dc.identifier.epage2688en_HK
dc.identifier.isiWOS:000227098400004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, Z=35271180800en_HK
dc.identifier.scopusauthoridZhang, L=8783285300en_HK
dc.identifier.scopusauthoridQin, C=7102688076en_HK
dc.identifier.scopusauthoridBa, L=8557032300en_HK
dc.identifier.scopusauthoridYi, CE=8557032800en_HK
dc.identifier.scopusauthoridZhang, F=10640508100en_HK
dc.identifier.scopusauthoridWei, Q=7201692917en_HK
dc.identifier.scopusauthoridHe, T=16935084000en_HK
dc.identifier.scopusauthoridYu, W=7403914045en_HK
dc.identifier.scopusauthoridYu, J=7405525088en_HK
dc.identifier.scopusauthoridGao, H=7402971042en_HK
dc.identifier.scopusauthoridTu, X=8789266900en_HK
dc.identifier.scopusauthoridGettie, A=7003730114en_HK
dc.identifier.scopusauthoridFarzan, M=7003535041en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridHo, DD=7402971998en_HK

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