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: Sung-Youl Ko, Hyun-Jeong Ko, Woo-Sung Chang, Se-Ho Park, Mi-Na Kweon, Chang-Yuil Kang
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 5 Pg. 3309-17 (Sep 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16116223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, CD1
• Antigens, CD1d
• Cancer Vaccines
• Cytokines
• Galactosylceramides
• Immunoglobulin A, Secretory
• Immunoglobulin G
• Viral Vaccines
• alpha-galactosylceramide
• Ovalbumin

Topics

• Adjuvants, Immunologic (pharmacology)
• Administration, Intranasal
• Animals
• Antigens, CD1 (physiology)
• Antigens, CD1d
• Cancer Vaccines (administration & dosage)
• Cytokines (biosynthesis)
• Defective Viruses (immunology)
• Female
• Galactosylceramides (pharmacology)
• Immunoglobulin A, Secretory (biosynthesis)
• Immunoglobulin G (biosynthesis)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasms, Experimental (immunology)
• Orthomyxoviridae Infections (prevention & control)
• Ovalbumin (immunology)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Vaccines (administration & dosage)