TY - JOUR
T1 - α-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor
AU - Ko, Sung Youl
AU - Ko, Hyun Jeong
AU - Chang, Woo Sung
AU - Park, Se Ho
AU - Kweon, Mi Na
AU - Kang, Chang Yuil
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=23844523426&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.175.5.3309
DO - 10.4049/jimmunol.175.5.3309
M3 - Article
C2 - 16116223
AN - SCOPUS:23844523426
SN - 0022-1767
VL - 175
SP - 3309
EP - 3317
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -