中文摘要：本研究的重点是在不改变外膜囊泡（OMV）免疫原性的情况下降低外膜囊泡（OMV）介导的毒性作用。研究选用了维生素A的活性代谢物全反视黄酸（ATRA），该视黄酸既具有抗炎作用又具备粘膜佐剂特性。体外和体内试验表明，采用ATRA预处理可以显著降低CPMVs诱导的TLR2介导的促炎性反应。同时，ATRA预处理后，口服双倍剂量的CPMVs（75 mu g)）能显著诱导产生粘膜免疫反应和保护效率。该结果可为降低OMV疫苗的毒性，诱导产生更好的免疫保护反应提供帮助。
外文摘要：Bacterial outer membrane vesicles have been extensively investigated and considered as a next generation vaccine. Recently, we have demonstrated that the cholera pentavalent outer membrane vesicles (CPMVs) immunogen induced adaptive immunity and had a strong protective efficacy against the circulating V. cholerae strains in a mouse model. In this present study, we are mainly focusing on reducing outer membrane vesicle (OMV) -mediated toxicity without altering its antigenic property. Therefore, we have selected All-trans Retinoic Acid (ATRA), active metabolites of vitamin A, which have both anti-inflammatory and mucosal adjuvant properties. Pre-treatment of ATRA significantly reduced CPMVs induced TLR2 mediated pro-inflammatory responses in vitro and in vivo. Furthermore, we also found ATRA pre-treatment significantly induced mucosal immune response and protective efficacy after two doses of oral immunization with CPMVs (75 mu g). This study can help to reduce OMV based vaccine toxicity and induce better protective immunity where children and men suffered from malnutrition mainly in developing countries.
外文关键词：ATRA； Cholera； CPMVs； OMVs； TLR2
作者：Sinha, R; Howlader, DR; Ta, A; Mitra, S; Das, S; Koley, H
作者单位：印度国立霍乱和肠道疾病研究所
期刊名称：VACCINE
期刊影响因子：3.325
出版年份：2017
出版刊次：6
点击下载：视黄酸能够下调霍乱弧菌外膜囊泡对急性炎症的诱导作用，增强粘膜免疫