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Journal of Virology, June 2009, p. 5726-5734, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00207-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge{triangledown}

Lucy A. Perrone,1 Attiya Ahmad,2 Vic Veguilla,1 Xiuhua Lu,1 Gale Smith,2 Jacqueline M. Katz,1 Peter Pushko,2 and Terrence M. Tumpey1*

Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Collaborating Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,1 Novavax, Inc., Rockville, Maryland2

Received 28 January 2009/ Accepted 17 March 2009

Influenza vaccines capable of inducing cross-reactive or heterotypic immunity could be an important first line of prevention against a novel subtype virus. Influenza virus-like particles (VLPs) displaying functional viral proteins are effective vaccines against replication-competent homologous virus, but their ability to induce heterotypic immunity has not been adequately tested. To measure VLP vaccine efficacy against a known influenza pandemic virus, recombinant VLPs were generated from structural proteins of the 1918 H1N1 virus. Mucosal and traditional parenteral administrations of H1N1 VLPs were compared for the ability to protect against the reconstructed 1918 virus and a highly pathogenic avian H5N1 virus isolated from a fatal human case. Mice that received two intranasal immunizations of H1N1 VLPs were largely protected against a lethal challenge with both the 1918 virus and the H5N1 virus. In contrast, mice that received two intramuscular immunizations of 1918 VLPs were only protected against a homologous virus challenge. Mucosal vaccination of mice with 1918 VLPs induced higher levels of cross-reactive immunoglobulin G (IgG) and IgA antibodies than did parenteral vaccination. Similarly, ferrets mucosally vaccinated with 1918 VLPs completely survived a lethal challenge with the H5N1 virus, while only a 50% survival rate was observed in parenterally vaccinated animals. These results suggest a strategy of VLP vaccination against a pandemic virus and one that stimulates heterotypic immunity against an influenza virus strain with threatening pandemic potential.

* Corresponding author. Mailing address: 1600 Clifton Rd. NE, MS G-16, Atlanta, GA 30333. Phone: (404) 639-5444. Fax: (404) 639-2350. E-mail: tft9{at}cdc.gov

{triangledown} Published ahead of print on 25 March 2009.

Journal of Virology, June 2009, p. 5726-5734, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00207-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Belyakov, I. M., Ahlers, J. D. (2009). What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?. J. Immunol. 183: 6883-6892 [Abstract] [Full Text]  


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