Mucosal vaccination approach against mosquito-borne Japanese encephalitis virus.
Mucosal vaccination approach against mosquito-borne Japanese encephalitis virus.
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DOI：
10.7883/yoken.jjid.2009.37
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发表时间：
2009-01
影响因子：
2.2
通讯作者：
T. Harakuni;H. Kohama;M. Tadano;Gen‐ichiro Uechi;N. Tsuji;Y. Matsumoto;T. Miyata;T. Tsuboi;H. Oku;T. Arakawa
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文献类型：
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作者：
T. Harakuni;H. Kohama;M. Tadano;Gen‐ichiro Uechi;N. Tsuji;Y. Matsumoto;T. Miyata;T. Tsuboi;H. Oku;T. Arakawa
为了研究粘膜疫苗对粘膜无关病原体的潜在适用性，采用非肠道疫苗接种方法作为预防蚊媒日本脑炎病毒（JEV）的策略。鼻内（i.n.）用小鼠脑衍生的福尔马林灭活的JE疫苗免疫在小鼠中诱导了强的病毒中和抗体，并且这种诱导通过与霍乱毒素（CT）和百日咳毒素共同施用而增强，但不与杀死的百日咳博德特氏菌（Bordetella pertussis）共同施用。由i.n.接种含有细菌毒素的JE疫苗的强度与肠外免疫方案诱导的强度相当，并且前者在迟发型超敏反应和局部抗体反应方面更有效。此外，细菌毒素的佐剂作用对粘膜途径比肠外途径更显著。另外两种非侵入性途径，口服和经皮给药，进行了检查，但i.n.这条路是迄今为止最有效的。最后，CT的B亚基和JEV包膜蛋白之间的嵌合融合蛋白的疫苗效力显示了非侵入性JE疫苗的发展的一些希望。我们的结果表明，粘膜疫苗接种方法对于非粘膜病原体（例如JEV）是可行的，但必须优化佐剂、载体分子和给药途径才能构建有效的疫苗平台。
To investigate the potential applicability of mucosal vaccines against mucosa-unrelated pathogens, a non-parenteral vaccination approach was taken as a prophylactic strategy against mosquito-borne Japanese encephalitis virus (JEV). Intranasal (i.n.) immunization with a mouse brain-derived formalin-inactivated JE vaccine induced a robust virus-neutralizing antibody in mice, and this induction was augmented by co-administration with cholera toxin (CT) and pertussis toxin, but not with killed Bordetella pertussis. The antibody response induced by the i.n. administration of the JE vaccine with bacterial toxins was comparable in intensity to that induced by a parenteral immunization regime, and the former was considerably more effective in terms of delayed-type hypersensitivity and local antibody response. In addition, the adjuvant effects of bacterial toxins were much more prominent for the mucosal than the parenteral route. Two other non-invasive routes, oral and transcutaneous administration, were examined, but the i.n. route was by far the most effective. Finally, the vaccine efficacy of a chimeric fusion protein between the B subunit of CT and the JEV envelope protein showed some promise for the development of non-invasive JE vaccine. Our results suggest that the mucosal vaccination approach is feasible for a non-mucosal pathogen such as JEV, but that the adjuvant, carrier molecule, and administration route must be optimized for construction of an effective vaccine platform.