α-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor
α-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor
复制标题
DOI：
10.4049/jimmunol.175.5.3309
复制
发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Kang, CY
中科院分区：
文献类型：
--
作者：
Ko, SY;Ko, HJ;Kang, CY
α-半乳糖神经酰胺（α-GalCer）是恒定V α 14（+）NKT细胞的配体，并由APC上的CD 1d分子呈递。NKT细胞响应于α-GalCer呈递的APC产生大量的Th 1和Th 2细胞因子。在这项研究中，我们评估了α-GalCer是否可以作为粘膜疫苗的有效鼻疫苗佐剂，其能够诱导全身以及粘膜免疫应答。当α-GalCer与OVA一起通过鼻内途径给予C57 BL/6和BALB/c小鼠时，在两种小鼠品系中观察到的混合Th 1和Th 2细胞因子谱诱导了显著的OVA特异性粘膜分泌伊加、全身IgG和CTL应答。有趣的是，当用分离自流感病毒A/PR/8/34的PR 8血凝素Ag与α-GalCer一起鼻内免疫BALB/c小鼠时，提供了针对流感病毒感染的显著保护。当alpha-GalCer与复制缺陷型活腺病毒共免疫BALB/c小鼠时，它显著诱导了Immoral和细胞免疫应答。此外，在C57 BL/6中，OVA与α-GalCer的鼻内施用显示针对EG 7肿瘤攻击的完全保护。在CD 1d（-/-）小鼠中，与α-GalCer鼻内联合给药诱导的佐剂效应被阻断，表明免疫应答仅由APC上的CD 1d分子介导。最有趣的是，当CFSE标记的OT-1细胞过继转移到同基因小鼠中时，鼻内共同施用的α-GalCer激活幼稚T细胞并触发它们分化成功能性效应T细胞。总的来说，我们的结果首次表明α-GalCer可以作为鼻疫苗佐剂，诱导针对病毒感染和肿瘤的保护性免疫应答。
alpha-Galactosylceramide (alpha-GalCer) is a ligand of invariant V alpha 14(+) 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 a-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 a-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 Immoral and cellular immune responses. In addition, intranasal administration of OVA with a-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 a-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors.