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Journal of Virology, May 2009, p. 5192-5203, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02081-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nonreplicating Vaccinia Virus Vectors Expressing the H5 Influenza Virus Hemagglutinin Produced in Modified Vero Cells Induce Robust Protection

Josef Mayrhofer,¹ Sogue Coulibaly,¹ Annett Hessel,¹ Georg W. Holzer,¹ Michael Schwendinger,¹ Peter Brühl,¹ Marijan Gerencer,¹ Brian A. Crowe,¹ Shen Shuo,² Wanjing Hong,² Yee Joo Tan,² Barbara Dietrich,¹ Nicolas Sabarth,¹ Helga Savidis-Dacho,¹ Otfried Kistner,¹ P. Noel Barrett,¹ and Falko G. Falkner^1*

Baxter Bioscience, Biomedical Research Center, Uferstrasse 15. A-2304 Orth/Donau, Austria,¹ Collaborative Anti-Viral Research Group, Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673²

Received 3 October 2008/ Accepted 3 February 2009

The timely development of safe and effective vaccines against avian influenza virus of the H5N1 subtype will be of the utmost importance in the event of a pandemic. Our aim was first to develop a safe live vaccine which induces both humoral and cell-mediated immune responses against human H5N1 influenza viruses and second, since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic, an egg-independent production procedure based on a permanent cell line. In the present article, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia virus vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain. This experimental vaccine was compared with a formalin-inactivated whole-virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high-dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain. A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole-virus vaccine, the dVV-HA5 vaccine induced substantial amounts of gamma interferon-secreting CD8 T cells. Thus, the nonreplicating recombinant vaccinia virus vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.

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* Corresponding author. Mailing address: Baxter Bioscience, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau, Austria. Phone: 43-1-20100-4232. Fax: 43-1-20100-4000. E-mail: falknef{at}baxter.com

Published ahead of print on 11 March 2009.

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Journal of Virology, May 2009, p. 5192-5203, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02081-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.