Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.1012457108
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dc.titleFeasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development
dc.contributor.authorDucatez, M.F.
dc.contributor.authorBahl, J.
dc.contributor.authorGriffin, Y.
dc.contributor.authorStigger-Rosser, E.
dc.contributor.authorFranks, J.
dc.contributor.authorBarman, S.
dc.contributor.authorVijaykrishna, D.
dc.contributor.authorWebb, A.
dc.contributor.authorGuan, Y.
dc.contributor.authorWebster, R.G.
dc.contributor.authorSmith, G.J.D.
dc.contributor.authorWebby, R.J.
dc.date.accessioned2016-06-01T10:25:17Z
dc.date.available2016-06-01T10:25:17Z
dc.date.issued2011-01-04
dc.identifier.citationDucatez, M.F., Bahl, J., Griffin, Y., Stigger-Rosser, E., Franks, J., Barman, S., Vijaykrishna, D., Webb, A., Guan, Y., Webster, R.G., Smith, G.J.D., Webby, R.J. (2011-01-04). Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development. Proceedings of the National Academy of Sciences of the United States of America 108 (1) : 349-354. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.1012457108
dc.identifier.issn00278424
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/124665
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.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1073/pnas.1012457108
dc.sourceScopus
dc.subjectCross-reactive
dc.subjectPandemic
dc.subjectUniversal
dc.typeArticle
dc.contributor.departmentDUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE
dc.description.doi10.1073/pnas.1012457108
dc.description.sourcetitleProceedings of the National Academy of Sciences of the United States of America
dc.description.volume108
dc.description.issue1
dc.description.page349-354
dc.description.codenPNASA
dc.identifier.isiut000285915000065
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