Abstract
alpha-Galactosylceramide (alpha-GalCer), originally isolated from a marine sponge, was known to activate natural killer T (NKT) cells through CD1d-mediated Ag presentation and induce Th1 and/or Th2 immunity. In this study, we evaluated the nasal adjuvanticity of alpha-GalCer when co-administered with formalin-inactivated influenza virus A/PR/8/34 (PR8) in BALB/c mice. A single nasal immunization of inactivated PR8 and alpha-GalCer induced brisk levels of PR8-specific IgG and IgA Abs in serum and lung washes. Antigen-specific Ab responses lasted for 3 months, providing protective immunity against challenge with live PR8. In addition, mice given alpha-GalCer also exhibited cellular immune responses including cytotoxic T lymphocyte (CTL) generation. Because it did not redirect Ags into brain, alpha-GalCer would likely pose no risk if administered as a nasal adjuvant. These results suggest for the first time that a single nasal immunization of inactivated virus and alpha-GalCer is a safe and effective means of preventing influenza infection.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intranasal
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Animals
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Antibody Formation / immunology
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Central Nervous System / immunology*
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Cytokines / metabolism
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Cytotoxicity, Immunologic / immunology
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Female
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Galactosylceramides / administration & dosage
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Galactosylceramides / immunology*
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Immunity, Cellular / immunology
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Immunization / methods
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / immunology*
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Kaplan-Meier Estimate
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Lymphocytes / cytology
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Lymphocytes / immunology
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Lymphocytes / metabolism
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Mice
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Mice, Inbred BALB C
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Orthomyxoviridae / immunology*
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Orthomyxoviridae Infections / virology
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Th2 Cells / cytology
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Time Factors
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Vaccines, Inactivated / administration & dosage
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Vaccines, Inactivated / immunology*
Substances
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Cytokines
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Galactosylceramides
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Influenza Vaccines
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Vaccines, Inactivated
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alpha-galactosylceramide