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Article: A recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses
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TitleA recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses
 
AuthorsDu, L4
Leung, VHC2
Zhang, X4
Zhou, J2
Chen, M2
He, W4
Zhang, HY2
Chan, CCS2
Poon, VKM2
Zhao, G1
Sun, S1
Cai, L4
Zhou, Y1
Zheng, BJ2
Jiang, S4 3
 
Issue Date2011
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2011, v. 6 n. 1 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0016555
 
AbstractDevelopment of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus. © 2011 Du et al.
 
ISSN1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0016555
 
PubMed Central IDPMC3029370
 
ISI Accession Number IDWOS:000286663900070
Funding AgencyGrant Number
New York Blood CenterNYB000068
Research Fund for the Control of Infectious Diseases
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 an intramural fund of the New York Blood Center (NYB000068), 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDu, L
 
dc.contributor.authorLeung, VHC
 
dc.contributor.authorZhang, X
 
dc.contributor.authorZhou, J
 
dc.contributor.authorChen, M
 
dc.contributor.authorHe, W
 
dc.contributor.authorZhang, HY
 
dc.contributor.authorChan, CCS
 
dc.contributor.authorPoon, VKM
 
dc.contributor.authorZhao, G
 
dc.contributor.authorSun, S
 
dc.contributor.authorCai, L
 
dc.contributor.authorZhou, Y
 
dc.contributor.authorZheng, BJ
 
dc.contributor.authorJiang, S
 
dc.date.accessioned2011-07-27T01:31:12Z
 
dc.date.available2011-07-27T01:31:12Z
 
dc.date.issued2011
 
dc.description.abstractDevelopment of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus. © 2011 Du et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2011, v. 6 n. 1 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0016555
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0016555
 
dc.identifier.epagee16555
 
dc.identifier.hkuros188640
 
dc.identifier.isiWOS:000286663900070
Funding AgencyGrant Number
New York Blood CenterNYB000068
Research Fund for the Control of Infectious Diseases
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 an intramural fund of the New York Blood Center (NYB000068), 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
dc.identifier.issn1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3029370
 
dc.identifier.pmid21304591
 
dc.identifier.scopuseid_2-s2.0-79551557170
 
dc.identifier.spagee16555
 
dc.identifier.urihttp://hdl.handle.net/10722/135281
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCross Protection
 
dc.subject.meshImmunoglobulin Fc Fragments - chemistry - immunology
 
dc.subject.meshInfluenza A Virus, H5N1 Subtype - chemistry - immunology
 
dc.subject.meshInfluenza Vaccines
 
dc.subject.meshVaccines, Synthetic - chemistry - immunology
 
dc.titleA recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses
 
dc.typeArticle
 
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Author Affiliations
  1. Institute of Microbiology Chinese Academy of Sciences
  2. The University of Hong Kong
  3. Fudan University Shanghai Medical College
  4. New York Blood Center