Article: Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity

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TitleRecombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity
AuthorsDu, L3
Zhao, G1 2
Chan, CCS2
Sun, S1
Chen, M2
Liu, Z3
Guo, H3
He, Y3
Zhou, Y1
Zheng, BJ2
Jiang, S3
KeywordsNeutralizing antibody
Protective immunity
Receptor-binding domain
SARS-CoV
Subunit vaccines
Issue Date2009
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviro
CitationVirology, 2009, v. 393 n. 1, p. 144-150 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.virol.2009.07.018
AbstractSevere acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells. © 2009 Elsevier Inc. All rights reserved.
ISSN0042-6822
2011 Impact Factor: 3.351
2011 SCImago Journal Rankings: 0.355
DOIhttp://dx.doi.org/10.1016/j.virol.2009.07.018
ISI Accession Number IDWOS:000270453600018
Funding AgencyGrant Number
National Institutes of Health (NIH) of the United StatesR01 AI68002
Control of Infectious Diseases, the Health, Welfare and Food Bureau of the Hong Kong SAR Government
National 973 Basic Research Program of China2005CB523001
Funding Information:

This study was supported by the National Institutes of Health (NIH) of the United States (R01 AI68002), by the Research Fund for the Control of Infectious Diseases, the Health, Welfare and Food Bureau of the Hong Kong SAR Government, and by the National 973 Basic Research Program of China (2005CB523001).

PubMed Central IDPMC2753736
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorDu, L
dc.contributor.authorZhao, G
dc.contributor.authorChan, CCS
dc.contributor.authorSun, S
dc.contributor.authorChen, M
dc.contributor.authorLiu, Z
dc.contributor.authorGuo, H
dc.contributor.authorHe, Y
dc.contributor.authorZhou, Y
dc.contributor.authorZheng, BJ
dc.contributor.authorJiang, S
dc.date.accessioned2010-10-31T11:13:26Z
dc.date.available2010-10-31T11:13:26Z
dc.date.issued2009
dc.description.abstractSevere acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells. © 2009 Elsevier Inc. All rights reserved.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationVirology, 2009, v. 393 n. 1, p. 144-150 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.virol.2009.07.018
dc.identifier.citeulike5475713
dc.identifier.doihttp://dx.doi.org/10.1016/j.virol.2009.07.018
dc.identifier.epage150
dc.identifier.hkuros175097
dc.identifier.isiWOS:000270453600018
Funding AgencyGrant Number
National Institutes of Health (NIH) of the United StatesR01 AI68002
Control of Infectious Diseases, the Health, Welfare and Food Bureau of the Hong Kong SAR Government
National 973 Basic Research Program of China2005CB523001
Funding Information:

This study was supported by the National Institutes of Health (NIH) of the United States (R01 AI68002), by the Research Fund for the Control of Infectious Diseases, the Health, Welfare and Food Bureau of the Hong Kong SAR Government, and by the National 973 Basic Research Program of China (2005CB523001).

dc.identifier.issn0042-6822
2011 Impact Factor: 3.351
2011 SCImago Journal Rankings: 0.355
dc.identifier.issue1
dc.identifier.openurl
dc.identifier.pmcidPMC2753736
dc.identifier.pmid19683779
dc.identifier.scopuseid_2-s2.0-70349383960
dc.identifier.spage144
dc.identifier.urihttp://hdl.handle.net/10722/125136
dc.identifier.volume393
dc.languageeng
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yviro
dc.publisher.placeUnited States
dc.relation.ispartofVirology
dc.relation.referencesReferences in Scopus
dc.subject.meshAntibodies, Viral - blood
dc.subject.meshMembrane Glycoproteins - genetics - immunology
dc.subject.meshSARS Virus - genetics - immunology
dc.subject.meshSevere Acute Respiratory Syndrome - immunology - prevention and control
dc.subject.meshViral Envelope Proteins - genetics - immunology
dc.subjectNeutralizing antibody
dc.subjectProtective immunity
dc.subjectReceptor-binding domain
dc.subjectSARS-CoV
dc.subjectSubunit vaccines
dc.titleRecombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity
dc.typeArticle
Author Affiliations
  1. Institute of Microbiology Chinese Academy of Sciences
  2. The University of Hong Kong
  3. New York Blood Center