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
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Administration, Intranasal
- Animals
- Antibody Formation / immunology
- Central Nervous System / immunology*
- Cytokines / metabolism
- Cytotoxicity, Immunologic / immunology
- Dose-Response Relationship, Drug
- Enzyme-Linked Immunosorbent Assay
- Female
- Galactosylceramides / administration & dosage
- Galactosylceramides / immunology*
- Immunity, Cellular / immunology
- Immunization / methods
- Influenza Vaccines / administration & dosage
- Influenza Vaccines / immunology*
- Kaplan-Meier Estimate
- Killer Cells, Natural / cytology
- Killer Cells, Natural / immunology
- Killer Cells, Natural / metabolism
- Lymphocytes / cytology
- Lymphocytes / immunology
- Lymphocytes / metabolism
- Mice
- Mice, Inbred BALB C
- Orthomyxoviridae / immunology*
- Orthomyxoviridae Infections / immunology
- Orthomyxoviridae Infections / prevention & control
- Orthomyxoviridae Infections / virology
- Th2 Cells / cytology
- Th2 Cells / immunology
- Th2 Cells / metabolism
- Time Factors
- Vaccines, Inactivated / administration & dosage
- Vaccines, Inactivated / immunology*
Substances
- Cytokines
- Galactosylceramides
- Influenza Vaccines
- Vaccines, Inactivated
- alpha-galactosylceramide