File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development

TitleFeasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development
Authors
KeywordsCross-reactive
Pandemic
Universal
Issue Date2011
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 1, p. 349-354 How to Cite?
AbstractSince the reemergence of highly pathogenic H5N1 influenza viruses in humans in 2003, these viruses have spread throughout avian species in Asia, Europe, and Africa. Their sustained circulation has resulted in the evolution of phylogenetically diverse lineages. Viruses from these lineages show considerable antigenic variation, which has confounded vaccine planning efforts. We reconstructed ancestral protein sequences at several nodes of the hemagglutinin (HA) and neuraminidase (NA) gene phylogenies that represent ancestors to diverse H5N1 virus clades. By using the same methods that have been used to generate currently licensed inactivated H5N1 vaccines, we were able to produce a panel of replication competent influenza viruses containing synthesized HA and NA genes representing the reconstructed ancestral proteins. We identified two of these viruses that showed promising in vitro cross-reactivity with clade 1, 2.1, 2.2, 2.3.4, and 4 viruses. To confirm that vaccine antigens derived from these viruses were able to elicit functional antibodies following immunization, we created whole-virus vaccines and compared their protective efficacy versus that of antigens from positive control, naturally occurring, and broadly reactive H5N1 viruses. The ancestral viruses' vaccines provided robust protection against morbidity and mortality in ferrets challenged with H5N1 strains from clades 1, 2.1, and 2.2 in a manner similar to those based on the control strains. These findings provide proof of principle that viable, computationally derived vaccine seed viruses can be constructed within the context of currently licensed vaccine platforms. Such technologies should be explored to enhance the cross reactivity and availability of H5N1 influenza vaccines.
Persistent Identifierhttp://hdl.handle.net/10722/142409
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institute of Allergy and Infectious DiseaseHHSN266200700005C
National Institute of Health, Department of Health and Human Services
American Lebanese Syrian Associated Charities
Agency for Science, Technology and Research, Singapore
Ministry of Health, Singapore
Funding Information:

From St. Jude Children's Research Hospital, we thank J. DeBeauchamp, D. Carey, and Dr. V. R. Pagala for excellent technical assistance; S. Krauss and D. Walker for providing reagents; A. C. Boon for critically reviewing the manuscript; and D. Galloway and K. Spelshouse for editorial and graphic assistance. We thank Drs. M. A. Ali, M. A. Kutkat, and M. Bahgat (Virology Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Giza, Egypt) for providing A/Turkey/Egypt/7/2007. This work and G.J.D.S.'s career development award were supported by Contract HHSN266200700005C from the National Institute of Allergy and Infectious Disease, National Institute of Health, Department of Health and Human Services, and by the American Lebanese Syrian Associated Charities. J.B., D.V., and G.J.D.S. are supported by the Duke-National University of Singapore Signature Research Program funded by the Agency for Science, Technology and Research, Singapore, and the Ministry of Health, Singapore.

References

 

DC FieldValueLanguage
dc.contributor.authorDucatez, MFen_HK
dc.contributor.authorBahl, Jen_HK
dc.contributor.authorGriffin, Yen_HK
dc.contributor.authorStiggerRosser, Een_HK
dc.contributor.authorFranks, Jen_HK
dc.contributor.authorBarman, Sen_HK
dc.contributor.authorVijaykrishna, Den_HK
dc.contributor.authorWebb, Aen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorWebster, RGen_HK
dc.contributor.authorSmith, GJDen_HK
dc.contributor.authorWebby, RJen_HK
dc.date.accessioned2011-10-28T02:45:26Z-
dc.date.available2011-10-28T02:45:26Z-
dc.date.issued2011en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 1, p. 349-354en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142409-
dc.description.abstractSince the reemergence of highly pathogenic H5N1 influenza viruses in humans in 2003, these viruses have spread throughout avian species in Asia, Europe, and Africa. Their sustained circulation has resulted in the evolution of phylogenetically diverse lineages. Viruses from these lineages show considerable antigenic variation, which has confounded vaccine planning efforts. We reconstructed ancestral protein sequences at several nodes of the hemagglutinin (HA) and neuraminidase (NA) gene phylogenies that represent ancestors to diverse H5N1 virus clades. By using the same methods that have been used to generate currently licensed inactivated H5N1 vaccines, we were able to produce a panel of replication competent influenza viruses containing synthesized HA and NA genes representing the reconstructed ancestral proteins. We identified two of these viruses that showed promising in vitro cross-reactivity with clade 1, 2.1, 2.2, 2.3.4, and 4 viruses. To confirm that vaccine antigens derived from these viruses were able to elicit functional antibodies following immunization, we created whole-virus vaccines and compared their protective efficacy versus that of antigens from positive control, naturally occurring, and broadly reactive H5N1 viruses. The ancestral viruses' vaccines provided robust protection against morbidity and mortality in ferrets challenged with H5N1 strains from clades 1, 2.1, and 2.2 in a manner similar to those based on the control strains. These findings provide proof of principle that viable, computationally derived vaccine seed viruses can be constructed within the context of currently licensed vaccine platforms. Such technologies should be explored to enhance the cross reactivity and availability of H5N1 influenza vaccines.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectCross-reactiveen_HK
dc.subjectPandemicen_HK
dc.subjectUniversalen_HK
dc.subject.meshAntigenic Variation - genetics-
dc.subject.meshCross Reactions - genetics-
dc.subject.meshEvolution, Molecular-
dc.subject.meshInfluenza A Virus, H5N1 Subtype - genetics - immunology-
dc.subject.meshPhylogeny-
dc.titleFeasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine developmenten_HK
dc.typeArticleen_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailSmith, GJD: gjsmith@hkucc1.hku.hken_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authoritySmith, GJD=rp00444en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1012457108en_HK
dc.identifier.pmid21173241en_HK
dc.identifier.pmcidPMC3017181-
dc.identifier.scopuseid_2-s2.0-78651097861en_HK
dc.identifier.hkuros196757en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78651097861&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume108en_HK
dc.identifier.issue1en_HK
dc.identifier.spage349en_HK
dc.identifier.epage354en_HK
dc.identifier.isiWOS:000285915000065-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDucatez, MF=10044731300en_HK
dc.identifier.scopusauthoridBahl, J=35308668200en_HK
dc.identifier.scopusauthoridGriffin, Y=36504219600en_HK
dc.identifier.scopusauthoridStiggerRosser, E=6503928369en_HK
dc.identifier.scopusauthoridFranks, J=12786180500en_HK
dc.identifier.scopusauthoridBarman, S=7102545572en_HK
dc.identifier.scopusauthoridVijaykrishna, D=12752817700en_HK
dc.identifier.scopusauthoridWebb, A=15047374900en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridWebster, RG=36048363100en_HK
dc.identifier.scopusauthoridSmith, GJD=8344015800en_HK
dc.identifier.scopusauthoridWebby, RJ=35448064800en_HK
dc.identifier.citeulike8507298-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats