Sublingual immunization with a live attenuated influenza A virus lacking the nonstructural protein 1 induces broad protective immunity in mice

Hae Jung Park, Boris Ferko, Young Ho Byun, Joo Hye Song, Gye Yeong Han, Elisabeth Roethl, Andrej Egorov, Thomas Muster, Baiklin Seong, Mi Na Kweon, Manki Song, Cecil Czerkinsky, Huan H. Nguyen

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Abstract

The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with live influenza virus has been found to be safe and effective for inducing protective immune responses in mucosal and systemic compartments. Here we demonstrate that SL immunization with NS1 deleted IAV (DeltaNS1 H1N1 or DeltaNS1 H5N1) induced protection against challenge with homologous as well as heterosubtypic influenza viruses. Protection was comparable with that induced by intranasal (IN) immunization and was associated with high levels of virus-specific antibodies (Abs). SL immunization with DeltaNS1 virus induced broad Ab responses in mucosal and systemic compartments and stimulated immune cells in mucosa-associated and systemic lymphoid organs. Thus, SL immunization with DeltaNS1 offers a novel potential vaccination strategy for the control of influenza outbreaks including pandemics.

Original languageEnglish
Article numbere39921
JournalPloS one
Volume7
Issue number6
DOIs
Publication statusPublished - 2012 Jun 27

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Park, H. J., Ferko, B., Byun, Y. H., Song, J. H., Han, G. Y., Roethl, E., Egorov, A., Muster, T., Seong, B., Kweon, M. N., Song, M., Czerkinsky, C., & Nguyen, H. H. (2012). Sublingual immunization with a live attenuated influenza A virus lacking the nonstructural protein 1 induces broad protective immunity in mice. PloS one, 7(6), [e39921]. https://doi.org/10.1371/journal.pone.0039921