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Article: Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection

TitleIntranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection
Authors
Issue Date2008
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal Of Immunology, 2008, v. 180 n. 2, p. 948-956 How to Cite?
Abstract
We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-γ-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile. Copyright © 2008 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/68213
ISSN
2013 Impact Factor: 5.362
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDu, Len_HK
dc.contributor.authorZhao, Gen_HK
dc.contributor.authorLin, Yen_HK
dc.contributor.authorSui, Hen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorMa, Sen_HK
dc.contributor.authorHe, Yen_HK
dc.contributor.authorJiang, Sen_HK
dc.contributor.authorWu, Cen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorZhou, Yen_HK
dc.contributor.authorZheng, BJen_HK
dc.date.accessioned2010-09-06T06:02:26Z-
dc.date.available2010-09-06T06:02:26Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Immunology, 2008, v. 180 n. 2, p. 948-956en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68213-
dc.description.abstractWe have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-γ-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile. Copyright © 2008 by The American Association of Immunologists, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.relation.ispartofJournal of Immunologyen_HK
dc.rightsThis is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (The AAI), publisher of The JI, holds the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). The AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org-
dc.subject.meshMembrane Glycoproteins - administration and dosage - genetics - immunology-
dc.subject.meshSARS Virus - drug effects - physiology-
dc.subject.meshSevere Acute Respiratory Syndrome - prevention and control-
dc.subject.meshViral Envelope Proteins - administration and dosage - genetics - immunology-
dc.subject.meshViral Vaccines - administration and dosage - genetics - immunology-
dc.titleIntranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infectionen_HK
dc.typeArticleen_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid18178835en_HK
dc.identifier.pmcidPMC2603051-
dc.identifier.scopuseid_2-s2.0-40449085104en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-40449085104&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume180en_HK
dc.identifier.issue2en_HK
dc.identifier.spage948en_HK
dc.identifier.epage956en_HK
dc.identifier.isiWOS:000252290000032-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDu, L=8686996200en_HK
dc.identifier.scopusauthoridZhao, G=8684553000en_HK
dc.identifier.scopusauthoridLin, Y=23479885500en_HK
dc.identifier.scopusauthoridSui, H=23971615600en_HK
dc.identifier.scopusauthoridChan, C=16021156900en_HK
dc.identifier.scopusauthoridMa, S=26028397100en_HK
dc.identifier.scopusauthoridHe, Y=8742157400en_HK
dc.identifier.scopusauthoridJiang, S=7404453146en_HK
dc.identifier.scopusauthoridWu, C=7501660961en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridZhou, Y=8791655300en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK

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