Sublingual vaccination with influenza virus protects mice against lethal viral infection

Joo Hye Song, Huan H. Nguyen, Nicolas Cuburu, Taisuke Horimoto, Sung Youl Ko, Se Ho Park, Cecil Czerkinsky, Mi Na Kweon

Research output: Contribution to journalArticlepeer-review

179 Citations (Scopus)


We assessed whether the sublingual (s.l.) route would be an effective means of delivering vaccines against influenza virus in mice by using either formalin-inactivated or live influenza A/PR/8 virus (H1N1). Sublingual administration of inactivated influenza virus given on two occasions induced both systemic and mucosal antibody responses and conferred protection against a lethal intranasal (i.n.) challenge with influenza virus. Coadministration of a mucosal adjuvant (mCTA-LTB) enhanced these responses and resulted in complete protection against respiratory viral challenge. In addition, s.l. administration of formalin-inactivated A/PR/8 plus mCTA-LTB induced systemic expansion of IFN-γ-secreting T cells and virus-specific cytotoxic T lymphocyte responses. Importantly, a single s.l. administration of live A/PR/8 virus was not pathogenic and induced protection mediated by both acquired and innate immunity. Moreover, s.l. administration of live A/PR/8 virus conferred heterosubtypic protection against respiratory challenge with H3N2 virus. Unlike the i.n. route, the A/PR/8 virus, whether live or inactivated, did not migrate to or replicate in the CNS after s.l. administration. Based on these promising findings, we propose that the s.l. mucosal route offers an attractive alternative to mucosal routes for administering influenza vaccines.

Original languageEnglish
Pages (from-to)1644-1649
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
Publication statusPublished - 2008 Feb 5


  • Intranasal
  • Mucosal adjuvant
  • Mucosal immunity
  • Redirection
  • Secretory IgA

ASJC Scopus subject areas

  • General


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