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The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate.
Vaccine 2006; 24(17):3669-76V

Abstract

The pandemic threat posed by highly pathogenic H5N1 influenza A viruses has created an urgent need for vaccines to protect against H5 virus infection. Because pathogenic viruses grow poorly in chicken eggs and their virulence poses a biohazard to vaccine producers, avirulent viruses produced by reverse genetics have become the preferred basis for vaccine production. Here, we investigated two key characteristics of potential H5 vaccine candidates: the hemaggutinin (HA) cleavage site sequence and its modification to attenuate virulence and the choice of background virus to provide a high-growth rate. We produced recombinant (6:2 reassortant) viruses that possessed a series of modified avirulent-type HA and neuraminidase genes, both of which were derived from an H5N1 human isolate. The other genes of these recombinant viruses were derived from donor virus strains known to grow well in eggs: the human strain A/Puerto Rico/8/34 (PR8) or an avian strain. All of the recombinant viruses grew well in eggs, were avirulent in chicks, and protected animals against infection with a wild-type virus. However, one of the recombinant viruses with an avian virus background acquired a mutation in the HA cleavage site sequence that conferred virulence potential to this virus. Moreover, vaccine candidates with the avian virus background were more virulent than those with the human virus background. We conclude that 6:2 recombinant viruses with a PR8 background are more suitable than those with an avian virus background for vaccine development and that the HA cleavage site sequence must be modified to minimize the potential for a vaccine virus to convert to a virulent form.

Authors+Show Affiliations

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. horimoto@ims.u-tokyo.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16378663

Citation

Horimoto, Taisuke, et al. "The Development and Characterization of H5 Influenza Virus Vaccines Derived From a 2003 Human Isolate." Vaccine, vol. 24, no. 17, 2006, pp. 3669-76.
Horimoto T, Takada A, Fujii K, et al. The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate. Vaccine. 2006;24(17):3669-76.
Horimoto, T., Takada, A., Fujii, K., Goto, H., Hatta, M., Watanabe, S., ... Kawaoka, Y. (2006). The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate. Vaccine, 24(17), pp. 3669-76.
Horimoto T, et al. The Development and Characterization of H5 Influenza Virus Vaccines Derived From a 2003 Human Isolate. Vaccine. 2006 Apr 24;24(17):3669-76. PubMed PMID: 16378663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate. AU - Horimoto,Taisuke, AU - Takada,Ayato, AU - Fujii,Ken, AU - Goto,Hideo, AU - Hatta,Masato, AU - Watanabe,Shinji, AU - Iwatsuki-Horimoto,Kiyoko, AU - Ito,Mutsumi, AU - Tagawa-Sakai,Yuko, AU - Yamada,Shinya, AU - Ito,Hirotoshi, AU - Ito,Toshihiro, AU - Imai,Masaki, AU - Itamura,Shigeyuki, AU - Odagiri,Takato, AU - Tashiro,Masato, AU - Lim,Wilina, AU - Guan,Yi, AU - Peiris,Malik, AU - Kawaoka,Yoshihiro, Y1 - 2005/07/21/ PY - 2005/01/11/received PY - 2005/03/29/revised PY - 2005/06/23/accepted PY - 2005/12/28/pubmed PY - 2006/6/16/medline PY - 2005/12/28/entrez SP - 3669 EP - 76 JF - Vaccine JO - Vaccine VL - 24 IS - 17 N2 - The pandemic threat posed by highly pathogenic H5N1 influenza A viruses has created an urgent need for vaccines to protect against H5 virus infection. Because pathogenic viruses grow poorly in chicken eggs and their virulence poses a biohazard to vaccine producers, avirulent viruses produced by reverse genetics have become the preferred basis for vaccine production. Here, we investigated two key characteristics of potential H5 vaccine candidates: the hemaggutinin (HA) cleavage site sequence and its modification to attenuate virulence and the choice of background virus to provide a high-growth rate. We produced recombinant (6:2 reassortant) viruses that possessed a series of modified avirulent-type HA and neuraminidase genes, both of which were derived from an H5N1 human isolate. The other genes of these recombinant viruses were derived from donor virus strains known to grow well in eggs: the human strain A/Puerto Rico/8/34 (PR8) or an avian strain. All of the recombinant viruses grew well in eggs, were avirulent in chicks, and protected animals against infection with a wild-type virus. However, one of the recombinant viruses with an avian virus background acquired a mutation in the HA cleavage site sequence that conferred virulence potential to this virus. Moreover, vaccine candidates with the avian virus background were more virulent than those with the human virus background. We conclude that 6:2 recombinant viruses with a PR8 background are more suitable than those with an avian virus background for vaccine development and that the HA cleavage site sequence must be modified to minimize the potential for a vaccine virus to convert to a virulent form. SN - 0264-410X UR - https://www.unboundmedicine.com/medline/citation/16378663/The_development_and_characterization_of_H5_influenza_virus_vaccines_derived_from_a_2003_human_isolate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(05)00621-3 DB - PRIME DP - Unbound Medicine ER -