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A recombinant influenza virus vaccine expressing the F protein of respiratory syncytial virus

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Abstract

Infections with influenza and respiratory syncytial virus (RSV) rank high among the most common human respiratory diseases worldwide. Previously, we developed a replication-incompetent influenza virus by replacing the coding sequence of the PB2 gene, which encodes one of the viral RNA polymerase subunits, with that of a reporter gene. Here, we generated a PB2-knockout recombinant influenza virus expressing the F protein of RSV (PB2-RSVF virus) and tested its potential as a bivalent vaccine. In mice intranasally immunized with the PB2-RSVF virus, we detected high levels of antibodies against influenza virus, but not RSV. PB2-RSVF virus-immunized mice were protected from a lethal challenge with influenza virus but experienced severe body weight loss when challenged with RSV, indicating that PB2-RSVF vaccination enhanced RSV-associated disease. These results highlight one of the difficulties of developing an effective bivalent vaccine against influenza virus and RSV infections.

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Acknowledgments

We thank Abigail Betanzos for her assistance during the project, and Susan Watson for editing the manuscript. This study was supported by a grant from the National Institute of Allergy and Infectious Disease, by a Grant-in-Aid for Specially Promoted Research, by a contract research fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases from the Ministry of Education, Culture, Sports, Science, and Technology, by grants-in-aid from the Ministry of Health, by ERATO (Japan Science and Technology Agency), and by the Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO). This work was, in part, also funded by the Institute of Science and Technology of Federal District Icyt-DF (project number, ICyT-DF23/2011). W.F. received financial support from the National Council on Science and Technology of Mexico (Conacyt-Mexico) and from the Fulbright-García Robles program.

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Authors and Affiliations

  1. Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Mexico

    Wendy Fonseca & Esther Orozco

  2. Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI, 53711, USA

    Wendy Fonseca, Makoto Ozawa, Masato Hatta & Yoshihiro Kawaoka

  3. Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan

    Makoto Ozawa & Yoshihiro Kawaoka

  4. Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan

    Makoto Ozawa

  5. Universidad Autónoma de la Ciudad de México, Mexico, Mexico

    Esther Orozco & Máximo B. Martínez

  6. Centro de Diagnóstico y Vigilancia epidemiológica del Distrito Federal, Mexico, Mexico

    Máximo B. Martínez

  7. ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan

    Yoshihiro Kawaoka

  8. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan

    Yoshihiro Kawaoka

Authors
  1. Wendy Fonseca
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  2. Makoto Ozawa
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  3. Masato Hatta
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  4. Esther Orozco
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  5. Máximo B. Martínez
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  6. Yoshihiro Kawaoka
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Corresponding authors

Correspondence to Makoto Ozawa or Yoshihiro Kawaoka.

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Fonseca, W., Ozawa, M., Hatta, M. et al. A recombinant influenza virus vaccine expressing the F protein of respiratory syncytial virus. Arch Virol 159, 1067–1077 (2014). https://doi.org/10.1007/s00705-013-1932-z

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  • DOI: https://doi.org/10.1007/s00705-013-1932-z

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