Sublingual immunization induces broad-based systemic and mucosal immune responses in mice

Vaccine. 2007 Dec 12;25(51):8598-610. doi: 10.1016/j.vaccine.2007.09.073. Epub 2007 Oct 25.


The potential of sublingual (s.l.) delivery of vaccine was examined in mice. We show the existence of a dense network of dendritic cells (DCs) in the s.l. epithelium and a rapid and transient increase in the frequency of s.l. DCs after topical application of cholera toxin (CT) adjuvant under the tongue. S.l. immunization with ovalbumin and CT induced vigorous systemic and mucosal antibody responses. Such treatment promoted mixed Th1 and Th2 cytokine responses and induced cytotoxic CD8(+) T cells in lung tissues and in systemic lymphoid organs. S.l. immunization was comparable to intranasal immunization and was superior to oral immunization regarding the magnitude and anatomic dissemination of the induced immune responses. S.l. administration of live influenza virus at a dose lethal by the nasal route was well tolerated and did not redirect virus to the olfactory bulb. These features underscore the potential of the s.l. mucosa to serve as an alternative vaccine delivery route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Sublingual
  • Adoptive Transfer
  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / biosynthesis
  • Antibody-Producing Cells
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cholera Toxin / immunology
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology
  • Dose-Response Relationship, Immunologic
  • Female
  • Flow Cytometry
  • Immunity, Mucosal / immunology*
  • Immunization / methods*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mouth Mucosa / cytology
  • Mouth Mucosa / immunology
  • Ovalbumin / immunology
  • Reverse Transcriptase Polymerase Chain Reaction


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Cytokines
  • Ovalbumin
  • Cholera Toxin