Sublingual immunization induces broad-based systemic and mucosal immune responses in mice.
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.
Cuburu
Nicolas
N
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 721, Université de Nice-Sophia Antipolis, Nice, France.
Kweon
Mi-Na
MN
Song
Joo-Hye
JH
Hervouet
Catherine
C
Luci
Carmelo
C
Sun
Jia-Bin
JB
Hofman
Paul
P
Holmgren
Jan
J
Anjuère
Fabienne
F
Czerkinsky
Cecil
C
D000276:Adjuvants, Immunologic; D000286:Administration, Sublingual; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000921:Antibody-Producing Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D010047:Ovalbumin; D002772:Cholera Toxin