A single intranasal immunization with inactivated influenza virus and alpha-galactosylceramide induces long-term protective immunity without redirecting antigen to the central nervous system.
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.
Youn
Hyun-Jun
HJ
Laboratory of Immunology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Ko
Sung-Youl
SY
Lee
Kyoo-A
KA
Ko
Hyun-Jeong
HJ
Lee
Yoon-Sook
YS
Fujihashi
Kohtaro
K
Boyaka
Prosper N
PN
Kim
Sang-Hee
SH
Horimoto
Taisuke
T
Kweon
Mi-Na
MN
Kang
Chang-Yuil
CY
D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*
D016207:Cytokines; D005699:Galactosylceramides; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C493154:alpha-galactosylceramide