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Influenza A and B viruses expressing altered NS1 proteins: A vaccine approach

  1. Peter Palese*‡
  1. *Department of Microbiology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029; and †Department of Dermatology, University of Vienna Medical School, Währinger Gürtel 18-20, 1090 Vienna, Austria

  1. Edited by Robert M. Chanock, National Institutes of Health, Bethesda, MD, and approved January 27, 2000 (received for review December 3, 1999)

Abstract

We propose a rational approach to the generation of live viral vaccines: alteration of virally encoded type I IFN antagonists to attenuate virulence while retaining immunogenicity. We have explored this concept by using the influenza virus. Previously we have shown that the NS1 protein of influenza A virus possesses anti-IFN activity. We now present evidence that influenza A and B viruses encoding altered viral NS1 proteins are highly attenuated in the mouse host, yet provide protection from challenge with wild-type viruses.

Footnotes

    • ↵‡ To whom reprint requests should be addressed. E-mail: peter.palese{at}mssm.edu.

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

    • Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.070525997.

    • Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.070525997

  • Abbreviations

    MDCK cells,
    Madin–Darby canine kidney cells;
    MOI,
    multiplicity of infection;
    pfu,
    plaque-forming unit;
    NEP,
    nuclear export protein;
    HA,
    hemagglutination;
    NP,
    nuclear protein
    • Received December 3, 1999.

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