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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

TitleA recombinant vaccine of H5N1 HA1 fused with foldon and human IgG Fc induced complete cross-clade protection against divergent H5N1 viruses
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 1 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/135281
ISSN
2014 Impact Factor: 3.234
2014 SCImago Journal Rankings: 1.300
PubMed Central ID
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorDu, Len_HK
dc.contributor.authorLeung, VHCen_HK
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorZhou, Jen_HK
dc.contributor.authorChen, Men_HK
dc.contributor.authorHe, Wen_HK
dc.contributor.authorZhang, HYen_HK
dc.contributor.authorChan, CCSen_HK
dc.contributor.authorPoon, VKMen_HK
dc.contributor.authorZhao, Gen_HK
dc.contributor.authorSun, Sen_HK
dc.contributor.authorCai, Len_HK
dc.contributor.authorZhou, Yen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorJiang, Sen_HK
dc.date.accessioned2011-07-27T01:31:12Z-
dc.date.available2011-07-27T01:31:12Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 1en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135281-
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.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
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 virusesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=6&issue=1&spage=e16555&epage=&date=2011&atitle=A+recombinant+vaccine+of+H5N1+HA1+fused+with+foldon+and+human+IgG+Fc+induced+complete+cross-clade+protection+against+divergent+H5N1+viruses-
dc.identifier.emailZhou, J:jiezhou@hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityZhou, J=rp01412en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0016555en_HK
dc.identifier.pmid21304591-
dc.identifier.pmcidPMC3029370-
dc.identifier.scopuseid_2-s2.0-79551557170en_HK
dc.identifier.hkuros188640en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79551557170&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue1en_HK
dc.identifier.spagee16555en_US
dc.identifier.epagee16555en_US
dc.identifier.isiWOS:000286663900070-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDu, L=8686996200en_HK
dc.identifier.scopusauthoridLeung, VHC=36612082100en_HK
dc.identifier.scopusauthoridZhang, X=36191535600en_HK
dc.identifier.scopusauthoridZhou, J=7405550443en_HK
dc.identifier.scopusauthoridChen, M=35168778400en_HK
dc.identifier.scopusauthoridHe, W=36993784800en_HK
dc.identifier.scopusauthoridZhang, HY=37662503200en_HK
dc.identifier.scopusauthoridChan, CCS=16021156900en_HK
dc.identifier.scopusauthoridPoon, VKM=54934161900en_HK
dc.identifier.scopusauthoridZhao, G=8684553000en_HK
dc.identifier.scopusauthoridSun, S=35171536200en_HK
dc.identifier.scopusauthoridCai, L=12807760400en_HK
dc.identifier.scopusauthoridZhou, Y=8791655300en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridJiang, S=35198433300en_HK

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