Hcp1-loaded staphylococcal membrane vesicle vaccine protects against acute melioidosis.
Hcp1-loaded staphylococcal membrane vesicle vaccine protects against acute melioidosis.
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DOI：
10.3389/fimmu.2022.1089225
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
类鼻疽伯克霍尔德氏菌是类鼻疽病的病原体，这是一种缺乏疫苗的致命热带传染病。在金黄色葡萄球菌RN 4220-Δagr（RN）减毒菌株的基础上，设计了RN 4220-Δagr/pdhB-hcp 1菌株（RN-Hcp 1），以产生B。类鼻疽溶血素共调节蛋白1（Hcp 1）负载的膜囊泡（hcp 1 MV）。hcp 1 MV与佐剂混合免疫BALB/c小鼠，可提高血清特异性IgG的产生。hcp 1 MV免疫小鼠的血清炎症因子水平（包括TNF-α和IL-6）与PBS攻击小鼠的水平相当。与接受重组Hcp 1蛋白（rHcp 1）或RN株衍生的MV（Δ agrMV）的小鼠相比，观察到葡萄球菌MV的部分佐剂效应，hcp 1 MV免疫小鼠的特异性抗体滴度升高。hcp 1 MV/佐剂疫苗保护70%的小鼠免受致死性B感染。假鼻疽攻毒。hcp 1 MVs免疫仅保护60%的小鼠，而rHcp 1或ΔagrMVs免疫则没有保护作用。此外，与其他组相比，接受hcp 1 MVs/佐剂和hcp 1 MVs免疫的小鼠具有较低的血清TNF-α和IL-6水平，并且没有炎症浸润。此外，hcp 1 MVs/佐剂组和hcp 1 MVs组中所有存活小鼠在感染后5天的肺、肝和脾中均未显示可培养细菌。总的来说，我们的数据强调了一种开发B的新策略。pseudomallei疫苗，并表明Hcp 1掺入的葡萄球菌MV是预防急性类鼻疽病的有希望的候选者。
Burkholderia pseudomallei is the causal agent of melioidosis, a deadly tropical infectious disease that lacks a vaccine. On the basis of the attenuated Staphylococcus aureus RN4220-Δagr (RN), we engineered the RN4220-Δagr/pdhB-hcp1 strain (RN-Hcp1) to generate B. pseudomallei hemolysin-coregulated protein 1 (Hcp1)-loaded membrane vesicles (hcp1MVs). The immunization of BALB/c mice with hcp1MVs mixed with adjuvant by a three-dose regimen increased the serum specific IgG production. The serum levels of inflammatory factors, including TNF-α and IL-6, in hcp1MV-vaccinated mice were comparable with those in PBS-challenged mice. The partial adjuvant effect of staphylococcal MVs was observed with the elevation of specific antibody titer in hcp1MV-vaccinated mice relative to those that received the recombinant Hcp1 protein (rHcp1) or MVs derived from RN strain (ΔagrMVs). The hcp1MVs/adjuvant vaccine protected 70% of mice from lethal B. pseudomallei challenge. Immunization with hcp1MVs only protected 60% of mice, whereas vaccination with rHcp1 or ΔagrMVs conferred no protection. Moreover, mice that received hcp1MVs/adjuvant and hcp1MVs immunization had low serum TNF-α and IL-6 levels and no inflammatory infiltration in comparison with other groups. In addition, all surviving mice in hcp1MVs/adjuvant and hcp1MVs groups exhibited no culturable bacteria in their lungs, livers, and spleens five days postinfection. Overall, our data highlighted a new strategy for developing B. pseudomallei vaccine and showed that Hcp1-incorporated staphylococcal MV is a promising candidate for the prevention of acute melioidosis.
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影响因子：
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影响因子：
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作者：
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发表时间：
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影响因子：
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