1. Evolutionary Biology
  2. Microbiology and Infectious Disease
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Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

  1. John Huddleston  Is a corresponding author
  2. John R Barnes
  3. Thomas Rowe
  4. Xiyan Xu
  5. Rebecca Kondor
  6. David E Wentworth
  7. Lynne Whittaker
  8. Burcu Ermetal
  9. Rodney Stuart Daniels
  10. John W McCauley
  11. Seiichiro Fujisaki
  12. Kazuya Nakamura
  13. Noriko Kishida
  14. Shinji Watanabe
  15. Hideki Hasegawa
  16. Ian Barr
  17. Kanta Subbarao
  18. Pierre Barrat-Charlaix
  19. Richard A Neher
  20. Trevor Bedford  Is a corresponding author
  1. University of Washington, United States
  2. Centers for Disease Control and Prevention (CDC), United States
  3. The Francis Crick Institute, United Kingdom
  4. The Francis Crick Insitute, United Kingdom
  5. National Institute of Infectious Diseases, Japan
  6. National Instituite of Infectious Diseases, Japan
  7. Peter Doherty Institute for Infection and Immunity, United States
  8. Peter Doherty Institute for Infection and Immunity, Australia
  9. University of Basel, Switzerland
  10. Fred Hutchinson Cancer Research Center, United States
Research Article
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Cite this article as: eLife 2020;9:e60067 doi: 10.7554/eLife.60067

Abstract

Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

Article and author information

Author details

  1. John Huddleston

    Molecular and Cell Biology, University of Washington, Seattle, United States
    For correspondence
    jlhudd@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4250-2063
  2. John R Barnes

    Virology Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Rowe

    Virology Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiyan Xu

    Virology Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rebecca Kondor

    Virology Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2596-4282
  6. David E Wentworth

    Virology Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases (NCIRD), Centers for Disease Control and Prevention (CDC), Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5190-980X
  7. Lynne Whittaker

    WHO Collaborating Centre for Reference and Research on Influenza, Crick Worldwide Influenza Centre, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Burcu Ermetal

    WHO Collaborating Centre for Reference and Research on Influenza, Crick Worldwide Influenza Centre, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Rodney Stuart Daniels

    Worldwide Influenza Centre, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. John W McCauley

    Worldwide Influenza Centre, The Francis Crick Insitute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4744-6347
  11. Seiichiro Fujisaki

    Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  12. Kazuya Nakamura

    Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  13. Noriko Kishida

    Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  14. Shinji Watanabe

    Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  15. Hideki Hasegawa

    Pathology, National Instituite of Infectious Diseases, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  16. Ian Barr

    World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Kanta Subbarao

    The WHO Collaborating Centre for Reference and Research on Influenza,, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1713-3056
  18. Pierre Barrat-Charlaix

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3816-3724
  19. Richard A Neher

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2525-1407
  20. Trevor Bedford

    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    tbedford@fhcrc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4039-5794

Funding

Cancer Research UK (FC001030)

  • Lynne Whittaker
  • Burcu Ermetal
  • Rodney Stuart Daniels
  • John W McCauley

National Institute of Allergy and Infectious Diseases (U19AI117891-01)

  • Trevor Bedford

National Institute of Allergy and Infectious Diseases (R01AI127893-01)

  • Pierre Barrat-Charlaix
  • Richard A Neher
  • Trevor Bedford

Medical Research Council (FC001030)

  • Lynne Whittaker
  • Burcu Ermetal
  • Rodney Stuart Daniels
  • John W McCauley

Wellcome (FC001030)

  • Lynne Whittaker
  • Burcu Ermetal
  • Rodney Stuart Daniels
  • John W McCauley

Ministry of Health, Labour and Welfare (10110400)

  • Seiichiro Fujisaki
  • Kazuya Nakamura
  • Noriko Kishida
  • Shinji Watanabe
  • Hideki Hasegawa

Japan Agency for Medical Research and Development (JPfk0108118)

  • Shinji Watanabe

Australian Government Department of Health

  • Ian Barr
  • Kanta Subbarao

National Institute of Allergy and Infectious Diseases (F31AI140714)

  • John Huddleston

National Institute of General Medical Sciences (R35GM119774-01)

  • Trevor Bedford

Pew Charitable Trusts

  • Trevor Bedford

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Vaughn S Cooper, University of Pittsburgh, United States

Publication history

  1. Received: June 17, 2020
  2. Accepted: August 24, 2020
  3. Accepted Manuscript published: September 2, 2020 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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