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Article: Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model

TitleReceptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model
Authors
Issue Date2007
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccine
Citation
Vaccine, 2007, v. 25 n. 15, p. 2832-2838 How to Cite?
AbstractDevelopment of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine. © 2006 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/78851
ISSN
2015 Impact Factor: 3.413
2015 SCImago Journal Rankings: 2.044
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDu, Len_HK
dc.contributor.authorZhao, Gen_HK
dc.contributor.authorHe, Yen_HK
dc.contributor.authorGuo, Yen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorJiang, Sen_HK
dc.contributor.authorZhou, Yen_HK
dc.date.accessioned2010-09-06T07:47:35Z-
dc.date.available2010-09-06T07:47:35Z-
dc.date.issued2007en_HK
dc.identifier.citationVaccine, 2007, v. 25 n. 15, p. 2832-2838en_HK
dc.identifier.issn0264-410Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/78851-
dc.description.abstractDevelopment of effective vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is still a priority in prevention of re-emergence of SARS. Our previous studies have shown that the receptor-binding domain (RBD) of SARS-CoV spike (S) protein elicits highly potent neutralizing antibody responses in the immunized animals. But it is unknown whether RBD can also induce protective immunity in an animal model, a key aspect for vaccine development. In this study, BALB/c mice were vaccinated intramuscularly (i.m.) with 10 μg of RBD-Fc (RBD fused with human IgG1 Fc) and boosted twice at 3-week intervals and one more time at 12th month. Humoral immune responses of vaccinated mice were investigated for up to 12 months at a 1-month interval and the neutralizing titers of produced antibodies were reported at months 0, 3, 6 and 12 post-vaccination. Mice were challenged with the homologous strain of SARS-CoV 5 days after the last boost, and sacrificed 5 days after the challenge. Mouse lung tissues were collected for detection of viral load, virus replication and histopathological effects. Our results showed that RBD-Fc vaccination induced high titer of S-specific antibodies with long-term and potent SARS-CoV neutralizing activity. Four of five vaccinated mice were protected from subsequent SARS-CoV challenge because no significant virus replication, and no obvious histopathological changes were found in the lung tissues of the vaccinated mice challenged with SARS-CoV. Only one vaccinated mouse had mild alveolar damage in the lung tissues. In contrast, high copies of SARS-CoV RNA and virus replication were detected, and pathological changes were observed in the lung tissues of the control mice. In conclusion, our findings suggest that RBD, which can induce protective antibodies to SARS-CoV, may be further developed as a safe and effective SARS subunit vaccine. © 2006 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccineen_HK
dc.relation.ispartofVaccineen_HK
dc.rightsVaccine. Copyright © Elsevier Ltd.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntibodies, Viral - biosynthesis - immunologyen_HK
dc.subject.meshAntibody Formation - immunologyen_HK
dc.subject.meshAntibody Specificityen_HK
dc.subject.meshCercopithecus aethiopsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshLung - pathologyen_HK
dc.subject.meshMembrane Glycoproteins - immunologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshPeptide Fragments - immunologyen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshSARS Virus - drug effects - immunology - physiologyen_HK
dc.subject.meshSevere Acute Respiratory Syndrome - immunology - prevention & controlen_HK
dc.subject.meshVaccines, Subunit - immunology - pharmacologyen_HK
dc.subject.meshVero Cellsen_HK
dc.subject.meshViral Envelope Proteins - immunologyen_HK
dc.subject.meshViral Vaccines - immunology - pharmacologyen_HK
dc.subject.meshVirus Replicationen_HK
dc.titleReceptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal modelen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0264-410X&volume=25&issue=15&spage=2832&epage=2838&date=2007&atitle=Receptor-binding+domain+of+SARS-CoV+spike+protein+induces+long-term+protective+immunity+in+an+animal+model.en_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.vaccine.2006.10.031en_HK
dc.identifier.pmid17092615en_HK
dc.identifier.scopuseid_2-s2.0-33947189535en_HK
dc.identifier.hkuros132262en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947189535&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue15en_HK
dc.identifier.spage2832en_HK
dc.identifier.epage2838en_HK
dc.identifier.isiWOS:000245825800012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridDu, L=8686996200en_HK
dc.identifier.scopusauthoridZhao, G=8684553000en_HK
dc.identifier.scopusauthoridHe, Y=8742157400en_HK
dc.identifier.scopusauthoridGuo, Y=8555122500en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridJiang, S=7404453146en_HK
dc.identifier.scopusauthoridZhou, Y=8791655300en_HK

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