title: alpha-Galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor.
abstract: alpha-Galactosylceramide (alpha-GalCer) is a ligand of invariant Valpha14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to alpha-GalCer-presented APC. In this study, we assessed whether alpha-GalCer could act as an effective nasal vaccine adjuvant for mucosal vaccine that would be capable of inducing systemic as well as mucosal immune responses. When alpha-GalCer was administered with OVA via the intranasal route to C57BL/6 and BALB/c mice, significant OVA-specific mucosal secretory IgA, systemic IgG, and CTL responses were induced with mixed Th1 and Th2 cytokine profiles seen in both strains of mice. Interestingly, as BALB/c mice were intranasally immunized with PR8 hemagglutinin Ag isolated from influenza virus A/PR/8/34 together with alpha-GalCer, significant protection was afforded against influenza viral infection. When alpha-GalCer was coimmunized with a replication-deficient live adenovirus to BALB/c mice, it significantly induced both humoral and cellular immune responses. In addition, intranasal administration of OVA with alpha-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with alpha-GalCer were blocked in CD1d-/- mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered alpha-GalCer activated naive T cells and triggered them to differentiate into functional effector T cells when CFSE-labeled OT-1 cells were adoptively transferred into syngeneic mice. Overall, our results are the first to show that alpha-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors.
authors.affiliation: Laboratory of Immunology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Ko
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Chang
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.forename: Chang-Yuil
authors.initials: CY
authors.lastname: Kang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D019496:Cancer Vaccines / Q000008:administration & dosage*; D016207:Cytokines / Q000096:biosynthesis; D003673:Defective Viruses / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D055610:Antigens, CD1d; D019496:Cancer Vaccines; D016207:Cytokines; D005699:Galactosylceramides; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014765:Viral Vaccines; C493154:alpha-galactosylceramide; D010047:Ovalbumin