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Research Article

Variable efficacy of repeated annual influenza vaccination

Derek J. Smith, Stephanie Forrest, David H. Ackley, and Alan S. Perelson
PNAS November 23, 1999 96 (24) 14001-14006; https://doi.org/10.1073/pnas.96.24.14001
Derek J. Smith
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Stephanie Forrest
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David H. Ackley
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Alan S. Perelson
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  1. Edited by Robert May, University of Oxford, Oxford, United Kingdom, and approved September 20, 1999 (received for review April 5, 1999)

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Abstract

Conclusions have differed in studies that have compared vaccine efficacy in groups receiving influenza vaccine for the first time to efficacy in groups vaccinated more than once. For example, the Hoskins study [Hoskins, T. W., Davis, J. R., Smith, A. J., Miller, C. L. & Allchin, A. (1979) Lancet i, 33–35] concluded that repeat vaccination was not protective in the long term, whereas the Keitel study [Keitel, W. A., Cate, T. R., Couch, R. B., Huggins, L. L. & Hess, K. R. (1997) Vaccine 15, 1114–1122] concluded that repeat vaccination provided continual protection. We propose an explanation, the antigenic distance hypothesis, and test it by analyzing seven influenza outbreaks that occurred during the Hoskins and Keitel studies. The hypothesis is that variation in repeat vaccine efficacy is due to differences in antigenic distances among vaccine strains and between the vaccine strains and the epidemic strain in each outbreak. To test the hypothesis, antigenic distances were calculated from historical hemagglutination inhibition assay tables, and a computer model of the immune response was used to predict the vaccine efficacy of individuals given different vaccinations. The model accurately predicted the observed vaccine efficacies in repeat vaccinees relative to the efficacy in first-time vaccinees (correlation 0.87). Thus, the antigenic distance hypothesis offers a parsimonious explanation of the differences between and within the Hoskins and Keitel studies. These results have implications for the selection of influenza vaccine strains, and also for vaccination strategies for other antigenically variable pathogens that might require repeated vaccination.

  • original antigenic sin
  • vaccine efficacy
  • repeated vaccination
  • antigenic distance

Footnotes

    • ↵§ To whom reprint requests should be addressed at: MS-K710, T-10, Los Alamos National Laboratory, Los Alamos, NM 87545. E-mail: asp{at}lanl.gov.

    • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviation

    HI,
    hemagglutination inhibition
    • Received April 5, 1999.
    • Copyright © 1999, The National Academy of Sciences
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    Variable efficacy of repeated annual influenza vaccination
    Derek J. Smith, Stephanie Forrest, David H. Ackley, Alan S. Perelson
    Proceedings of the National Academy of Sciences Nov 1999, 96 (24) 14001-14006; DOI: 10.1073/pnas.96.24.14001

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    Variable efficacy of repeated annual influenza vaccination
    Derek J. Smith, Stephanie Forrest, David H. Ackley, Alan S. Perelson
    Proceedings of the National Academy of Sciences Nov 1999, 96 (24) 14001-14006; DOI: 10.1073/pnas.96.24.14001
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    Proceedings of the National Academy of Sciences: 96 (24)
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