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霍乱弧菌五价外膜囊泡在成年和被动哺乳小鼠模型中诱导适应性免疫应答和保护效力。

Pentavalent outer membrane vesicles of Vibrio cholerae induce adaptive immune response and protective efficacy in both adult and passive suckling mice models.

机构信息

Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India.

Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India.

出版信息

Microbes Infect. 2015 Mar;17(3):215-27. doi: 10.1016/j.micinf.2014.10.011. Epub 2014 Nov 15.

Abstract

Recently, we demonstrated oral immunizations with single serotype outer membrane vesicles of Vibrio cholerae induced serogroup specific protective immunity in the RITARD model. In our present study, we advanced our research by formulating multi-serotype outer membrane vesicles, mixing the OMVs of five virulent V. cholerae strains. Four doses of oral immunization with cholera pentavalent outer membrane vesicles (CPMVs) induced V. cholerae specific B and T cell responses. CPMVs-immunized mice generated long lasting serum IgG, IgA, IgM as well as mucosal sIgA and also elicited a higher percentage of CD4+ T cell distribution in spleen. Our study revealed that in vitro CPMVs-activated dendritic cells were secreting T cell polarizing cytokines, IL-12p40, IL-4, IL-6 and IL-1β. Moreover, purified splenic CD4+ T cells of immunized mice also secreted IL-4, IL-13 and IL-17 cytokines, indicating the initiation of Th2 and Th17 cell mediated immune responses. CPMVs immunized adult female mice and their offspring were significantly protected from heterologous challenge with wild type V. cholerae. CPMVs could be exploited for the development of a novel non-living vaccine against circulating cholera in near future.

摘要

最近,我们通过使用霍乱弧菌单血清型外膜囊泡进行口服免疫,在 RITARD 模型中诱导了血清型特异性保护免疫。在本研究中,我们通过制备多血清型外膜囊泡,混合了五种毒力霍乱弧菌菌株的 OMVs,推进了我们的研究。用霍乱五价外膜囊泡(CPMVs)进行 4 次口服免疫可诱导霍乱弧菌特异性 B 和 T 细胞反应。CPMVs 免疫的小鼠产生了持久的血清 IgG、IgA、IgM 以及黏膜 sIgA,并且在脾脏中引发了更高比例的 CD4+T 细胞分布。我们的研究表明,体外 CPMVs 激活的树突状细胞分泌 T 细胞极化细胞因子,如 IL-12p40、IL-4、IL-6 和 IL-1β。此外,免疫小鼠的纯化脾 CD4+T 细胞也分泌了 IL-4、IL-13 和 IL-17 细胞因子,表明 Th2 和 Th17 细胞介导的免疫反应已经开始。CPMVs 免疫的成年雌性小鼠及其后代对野生型霍乱弧菌的异源攻击有明显的保护作用。CPMVs 可用于开发针对流行霍乱的新型非活疫苗。

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