Article: Molecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus

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TitleMolecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus
AuthorsFang, Y1 3 5
Rowe, T1 3
Leon, AJ3
Banner, D1
Danesh, A1 5
Xu, L1
Ran, L1
Bosinger, SE4
Guan, Y3
Chen, H3
Cameron, CC1
Cameron, MJ1
Kelvin, DJ1 2 3 5
Issue Date2010
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
CitationJournal Of Virology, 2010, v. 84 n. 17, p. 8369-8388 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.02305-09
AbstractThe 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODNadjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN-α2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freund's adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
ISSN0022-538X
2011 Impact Factor: 5.402
2011 SCImago Journal Rankings: 0.745
DOIhttp://dx.doi.org/10.1128/JVI.02305-09
ISI Accession Number IDWOS:000280605300002
Funding AgencyGrant Number
Li Ka Shing Foundation
Canadian Institute of Health Research
Sardegna Ricerche
National Institutes of Health
Funding Information:

This work is supported by grants from the Li Ka Shing Foundation, the Canadian Institute of Health Research, Sardegna Ricerche, and the National Institutes of Health.

PubMed Central IDPMC2919000
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorFang, Y
dc.contributor.authorRowe, T
dc.contributor.authorLeon, AJ
dc.contributor.authorBanner, D
dc.contributor.authorDanesh, A
dc.contributor.authorXu, L
dc.contributor.authorRan, L
dc.contributor.authorBosinger, SE
dc.contributor.authorGuan, Y
dc.contributor.authorChen, H
dc.contributor.authorCameron, CC
dc.contributor.authorCameron, MJ
dc.contributor.authorKelvin, DJ
dc.date.accessioned2010-10-31T11:14:14Z
dc.date.available2010-10-31T11:14:14Z
dc.date.issued2010
dc.description.abstractThe 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODNadjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN-α2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freund's adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationJournal Of Virology, 2010, v. 84 n. 17, p. 8369-8388 [How to Cite?]
DOI: http://dx.doi.org/10.1128/JVI.02305-09
dc.identifier.doihttp://dx.doi.org/10.1128/JVI.02305-09
dc.identifier.epage8388
dc.identifier.hkuros180506
dc.identifier.isiWOS:000280605300002
Funding AgencyGrant Number
Li Ka Shing Foundation
Canadian Institute of Health Research
Sardegna Ricerche
National Institutes of Health
Funding Information:

This work is supported by grants from the Li Ka Shing Foundation, the Canadian Institute of Health Research, Sardegna Ricerche, and the National Institutes of Health.

dc.identifier.issn0022-538X
2011 Impact Factor: 5.402
2011 SCImago Journal Rankings: 0.745
dc.identifier.issue17
dc.identifier.openurl
dc.identifier.pmcidPMC2919000
dc.identifier.pmid20534862
dc.identifier.scopuseid_2-s2.0-77956642388
dc.identifier.spage8369
dc.identifier.urihttp://hdl.handle.net/10722/125150
dc.identifier.volume84
dc.languageeng
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Virology
dc.relation.referencesReferences in Scopus
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.
dc.rightsCopyright © American Society for Microbiology, Journal of Virology, 2010, v. 84 n. 17, p. 8369-8688
dc.subject.meshFerrets
dc.subject.meshInfluenza A Virus, H1N1 Subtype - genetics - immunology - physiology
dc.subject.meshInfluenza Vaccines - administration and dosage - genetics - immunology
dc.subject.meshInfluenza, Human - immunology - prevention and control - virology
dc.subject.meshOligodeoxyribonucleotides - administration and dosage - immunology
dc.titleMolecular characterization of in vivo adjuvant activity in ferrets vaccinated against influenza virus
dc.typeArticle
Author Affiliations
  1. Toronto General Research Institute
  2. Università degli Studi di Sassari
  3. Shantou University, Medical College (SUMC)
  4. University of Pennsylvania
  5. University of Toronto