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Development of high-yield influenza A virus vaccine viruses

Author

Listed:
  • Jihui Ping

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison)

  • Tiago J.S. Lopes

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison
    The Institute of Medical Science, University of Tokyo)

  • Chairul A. Nidom

    (Avian Influenza-Zoonosis Research Center, Airlangga University)

  • Elodie Ghedin

    (New York University
    University of Pittsburgh School of Medicine)

  • Catherine A. Macken

    (Bioinformatics Institute, University of Auckland)

  • Adam Fitch

    (University of Pittsburgh School of Medicine)

  • Masaki Imai

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison)

  • Eileen A. Maher

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison)

  • Gabriele Neumann

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison)

  • Yoshihiro Kawaoka

    (School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison
    The Institute of Medical Science, University of Tokyo)

Abstract

Vaccination is one of the most cost-effective ways to prevent infection. Influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. Here, we screened A/Puerto Rico/8/34 (PR8) virus mutant libraries to develop vaccine backbones (defined here as the six viral RNA segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. We also tested mutations in the coding and regulatory regions of the virus, and chimeric haemagglutinin and neuraminidase genes. A combination of high-yield mutations from these screens led to a PR8 backbone that improved the titres of H1N1, H3N2, H5N1 and H7N9 vaccine viruses in African green monkey kidney and Madin–Darby canine kidney cells. This PR8 backbone also improves titres in embryonated chicken eggs, a common propagation system for influenza viruses. This PR8 vaccine backbone thus represents an advance in seasonal and pandemic influenza vaccine development.

Suggested Citation

  • Jihui Ping & Tiago J.S. Lopes & Chairul A. Nidom & Elodie Ghedin & Catherine A. Macken & Adam Fitch & Masaki Imai & Eileen A. Maher & Gabriele Neumann & Yoshihiro Kawaoka, 2015. "Development of high-yield influenza A virus vaccine viruses," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9148
    DOI: 10.1038/ncomms9148
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    Cited by:

    1. Osman Y. Özaltın & Oleg A. Prokopyev & Andrew J. Schaefer, 2018. "Optimal Design of the Seasonal Influenza Vaccine with Manufacturing Autonomy," INFORMS Journal on Computing, INFORMS, vol. 30(2), pages 371-387, May.
    2. Li, X. & Phillips, J.C., 2017. "Prediction (early recognition) of emerging flu strain clusters," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 479(C), pages 371-378.

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