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Proc Natl Acad Sci USA. Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development
Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development (PNAS, abstract, edited)
[Source: Proc Natl Acad Sci USA, full text <cite cite="http://www.pnas.org/content/108/1/349.short?rss=1">Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development ? PNAS</cite>. Abstract, edited.]
Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development
1. Mariette F. Ducatez a, 2. Justin Bahl b,c, 3. Yolanda Griffin a, 4. Evelyn Stigger-Rosser a, 5. John Franks a, 6. Subrata Barman a, 7. Dhanasekaran Vijaykrishna b,c, 8. Ashley Webb a, 9. Yi Guan c,d, 10. Robert G. Webster a, 11. Gavin J. D. Smith b,c, and 12. Richard J. Webby a,1
Author Affiliations
1. a Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-3678;
2. b Duke?National University of Singapore Graduate Medical School, Republic of Singapore 169857;
3. c State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, University of Hong Kong, Hong Kong, SAR, China; and
4. d International Institute of Infection and Immunity, Shantou University, Shantou 515031, China
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved November 16, 2010 (received for review August 23, 2010)
Abstract
Since 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.
* universal
* cross-reactive
* pandemic
Footnotes
* 1 To whom correspondence should be addressed. E-mail: richard.webby@stjude.org.
* Author contributions: M.F.D., G.J.D.S., and R.J.W. designed research; M.F.D., J.B., Y. Griffin, E.S.-R., J.F., S.B., D.V., and A.W. performed research; M.F.D. and R.J.W. analyzed data; and M.F.D., J.B., Y. Guan, R.G.W., G.J.D.S., and R.J.W. wrote the paper.
* The authors declare no conflict of interest.
* Data deposition: The sequences for A/turkey/Egypt/7/2007 reported in this paper have been deposited in the GenBank database (accession nos. CY055188?CY055195).
* This article is a PNAS Direct Submission.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
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[Source: Proc Natl Acad Sci USA, full text <cite cite="http://www.pnas.org/content/108/1/349.short?rss=1">Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development ? PNAS</cite>. Abstract, edited.]
Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development
1. Mariette F. Ducatez a, 2. Justin Bahl b,c, 3. Yolanda Griffin a, 4. Evelyn Stigger-Rosser a, 5. John Franks a, 6. Subrata Barman a, 7. Dhanasekaran Vijaykrishna b,c, 8. Ashley Webb a, 9. Yi Guan c,d, 10. Robert G. Webster a, 11. Gavin J. D. Smith b,c, and 12. Richard J. Webby a,1
Author Affiliations
1. a Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-3678;
2. b Duke?National University of Singapore Graduate Medical School, Republic of Singapore 169857;
3. c State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, University of Hong Kong, Hong Kong, SAR, China; and
4. d International Institute of Infection and Immunity, Shantou University, Shantou 515031, China
1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved November 16, 2010 (received for review August 23, 2010)
Abstract
Since 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.
* universal
* cross-reactive
* pandemic
Footnotes
* 1 To whom correspondence should be addressed. E-mail: richard.webby@stjude.org.
* Author contributions: M.F.D., G.J.D.S., and R.J.W. designed research; M.F.D., J.B., Y. Griffin, E.S.-R., J.F., S.B., D.V., and A.W. performed research; M.F.D. and R.J.W. analyzed data; and M.F.D., J.B., Y. Guan, R.G.W., G.J.D.S., and R.J.W. wrote the paper.
* The authors declare no conflict of interest.
* Data deposition: The sequences for A/turkey/Egypt/7/2007 reported in this paper have been deposited in the GenBank database (accession nos. CY055188?CY055195).
* This article is a PNAS Direct Submission.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
-
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