中文摘要：研究通过对脂多糖脂质A部分结构的修饰构建了一个低毒性的外嚢膜泡（fmOMV），分析了该外嚢膜泡作为肠道疫苗佐剂对流感疫苗的作用。与最初的OMV相比，fmOMV能够降低toll样受体4的活性，且毒性较弱。以fmOMV为佐剂进行肠道免疫能够显著提高机体抗体水平和T细胞反应，显著提高纵隔淋巴结中CD103(+)树状突细胞的数量，对小鼠产生更高的免疫保护作用。这些结果表明，fmOMV是肠道免疫有效的粘膜佐剂。
外文摘要：Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103(+) dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines.
外文关键词：Outer membrane vesicles；Influenza；Intranasal；Vaccine；Adjuvant；CD103(+) dendritic cells
作者：Lee, TY; Kim, CU; Bae, EH; Seo, SH; Jeong, DG; Yoon, SW; Chang, KT; Kim, YS; Kim, SH; Kim, DJ
作者单位：韩国生命工学研究院
期刊名称：VACCINE
期刊影响因子：3.413
出版年份：2017
出版刊次：1
点击下载：以小鼠为模型分析外膜囊泡包裹的脂质A对降低流感疫苗毒性的作用
