α-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor

Sung Youl Ko, Hyun Jeong Ko, Woo Sung Chang, Se Ho Park, Mi Na Kweon, Chang Yuil Kang

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

Abstract

α-Galactosylceramide (α-GalCer) is a ligand of invariant Vα14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to α-GalCer-presented APC. In this study, we assessed whether α-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 α-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 α-GalCer, significant protection was afforded against influenza viral infection. When α-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 α-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with α-GalCer were blocked in CD1d-/- mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered α-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 α-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors.

Original languageEnglish
Pages (from-to)3309-3317
Number of pages9
JournalJournal of Immunology
Volume175
Issue number5
DOIs
Publication statusPublished - 2005 Sep 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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