Sublingual vaccination with influenza virus protects mice against lethal viral infection
Sublingual vaccination with influenza virus protects mice against lethal viral infection
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DOI：
10.1073/pnas.0708684105
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发表时间：
2008-02-05
影响因子：
11.1
通讯作者：
Kweon, Mi-Na
中科院分区：
文献类型：
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作者：
Song, Joo-Hye;Nguyen, Huan H.;Kweon, Mi-Na
我们评估了舌下（s.l.）通过使用福尔马林灭活的或活的流感A/PR/8病毒（H1N1），该途径将是在小鼠中递送针对流感病毒的疫苗的有效手段。舌下给予灭活流感病毒两次诱导全身和粘膜抗体应答，并赋予针对致死性鼻内（i.n.）流感病毒的挑战。粘膜佐剂（mCTA-LTB）的共同管理增强了这些反应，并导致对呼吸道病毒攻击的完全保护。此外，s. l.施用福尔马林灭活的A/PR/8加mCTA-LTB诱导IFN-γ分泌性T细胞的全身扩增和病毒特异性细胞毒性T淋巴细胞应答。重要的是，一个单一的S. L.给予活的A/PR/8病毒不是致病性的，并且诱导由获得性和先天性免疫介导的保护。此外，s.l.给予活的A/PR/8病毒赋予针对H3 N2病毒的呼吸道攻击的异亚型保护。不像i.n.途径，A/PR/8病毒，无论是活的还是灭活的，在s.l.局基于这些有希望的发现，我们建议，s.l.粘膜途径为施用流感疫苗提供了粘膜途径的有吸引力的替代方案。
We assessed whether the sublingual (s.l.) route would be an effective means of delivering vaccines against influenza virus in mice by using either formalin-inactivated or live influenza A/PR/8 virus (H1N1). Sublingual administration of inactivated influenza virus given on two occasions induced both systemic and mucosal antibody responses and conferred protection against a lethal intranasal (i.n.) challenge with influenza virus. Coadministration of a mucosal adjuvant (mCTA-LTB) enhanced these responses and resulted in complete protection against respiratory viral challenge. In addition, s.l. administration of formalin-inactivated A/PR/8 plus mCTA-LTB induced systemic expansion of IFN-gamma-secreting T cells and virus-specific cytotoxic T lymphocyte responses. Importantly, a single s.l. administration of live A/PR/8 virus was not pathogenic and induced protection mediated by both acquired and innate immunity. Moreover, s.l. administration of live A/PR/8 virus conferred heterosubtypic protection against respiratory challenge with H3N2 virus. Unlike the i.n. route, the A/PR/8 virus, whether live or inactivated, did not migrate to or replicate in the CNS after s.l. administration. Based on these promising findings, we propose that the s.l. mucosal route offers an attractive alternative to mucosal routes for administering influenza vaccines.