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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
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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
 
AuthorsDu, L2 4
Zhao, G1
Lin, Y2
Sui, H2
Chan, C2
Ma, S2
He, Y4
Jiang, S4
Wu, C3
Yuen, KY2
Jin, DY2
Zhou, Y1
Zheng, BJ2
 
Issue Date2008
 
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
 
CitationJournal Of Immunology, 2008, v. 180 n. 2, p. 948-956 [How to Cite?]
 
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.
 
ISSN0022-1767
2013 Impact Factor: 5.362
 
PubMed Central IDPMC2603051
 
ISI Accession Number IDWOS:000252290000032
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDu, L
 
dc.contributor.authorZhao, G
 
dc.contributor.authorLin, Y
 
dc.contributor.authorSui, H
 
dc.contributor.authorChan, C
 
dc.contributor.authorMa, S
 
dc.contributor.authorHe, Y
 
dc.contributor.authorJiang, S
 
dc.contributor.authorWu, C
 
dc.contributor.authorYuen, KY
 
dc.contributor.authorJin, DY
 
dc.contributor.authorZhou, Y
 
dc.contributor.authorZheng, BJ
 
dc.date.accessioned2010-09-06T06:02:26Z
 
dc.date.available2010-09-06T06:02:26Z
 
dc.date.issued2008
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationJournal Of Immunology, 2008, v. 180 n. 2, p. 948-956 [How to Cite?]
 
dc.identifier.epage956
 
dc.identifier.isiWOS:000252290000032
 
dc.identifier.issn0022-1767
2013 Impact Factor: 5.362
 
dc.identifier.issue2
 
dc.identifier.pmcidPMC2603051
 
dc.identifier.pmid18178835
 
dc.identifier.scopuseid_2-s2.0-40449085104
 
dc.identifier.spage948
 
dc.identifier.urihttp://hdl.handle.net/10722/68213
 
dc.identifier.volume180
 
dc.languageeng
 
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Immunology
 
dc.relation.referencesReferences in Scopus
 
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 infection
 
dc.typeArticle
 
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Author Affiliations
  1. Institute of Microbiology Chinese Academy of Sciences
  2. The University of Hong Kong
  3. Sun Yat-Sen University
  4. New York Blood Center