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经鼻内接种的纳米乳剂佐剂疫苗（2C-葡萄球菌/纳米乳剂）对侵袭性肺炎的保护作用。

Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive pneumonia.

作者信息

Yang Liu-Yang, Zhou Heng, Yang Yun, Tong Ya-Nan, Peng Liu-Sheng, Zhu Bao-Hang, Diao Wei-Bo, Zeng Hao, Sun Hong-Wu, Zou Quan-Ming

机构信息

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University Chongqing 400038 PR China

出版信息

RSC Adv. 2018 Mar 12;8(18):9996-10008. doi: 10.1039/c7ra13630g. eCollection 2018 Mar 5.

DOI:10.1039/c7ra13630g
PMID:35540845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9078739/
Abstract

No licensed () vaccine is currently available. To develop an effective vaccine, we selected the recombinant proteins staphylococcal enterotoxin B (rSEB) and manganese transport protein C (rMntC) as vaccine candidates and formulated a 2C-Staph vaccine. Based on the optimised formation of nanoemulsion (NE) technology, we constructed a novel NE adjuvant vaccine, 2C-Staph/NE. The 2C-Staph/NE particles showed a suitable diameter (24.9 ± 0.14 nm), a good protein structure of integrity and specificity, and high thermodynamic stability. 2C-Staph formulated with an NE adjuvant induced higher survival rates than a 2C-Staph/MF59 vaccine in sepsis and pneumonia models. Moreover, intramuscular vaccination with 2C-Staph/NE yielded protection efficacy in a sepsis model, and the intranasal vaccination route induced a potent protective effect in a pneumonia model. Intranasal vaccination with 2C-Staph/NE induced a strong mucosal response with high levels of IgA and IL-17A in bronchoalveolar lavage fluid (BALF), and the IgG levels in the BALF were comparable to those induced by the intramuscular vaccination route. Furthermore, the serum and BALF induced by intranasal administration showed potent opsonophagocytic activity against . And, the IL-17A played a protective role in the pneumonia model demonstrated by a cytokine neutralization test. Taken together, our results showed that intranasal administration of 2C-Staph formulated with an NE adjuvant yielded ideal protection in a murine pneumonia model.

摘要

目前尚无获得许可的（）疫苗。为研发一种有效的疫苗，我们选择重组蛋白葡萄球菌肠毒素B（rSEB）和锰转运蛋白C（rMntC）作为候选疫苗，并配制了2C - 葡萄球菌疫苗。基于纳米乳剂（NE）技术的优化形成，我们构建了一种新型NE佐剂疫苗2C - 葡萄球菌/NE。2C - 葡萄球菌/NE颗粒显示出合适的直径（24.9±0.14纳米）、良好的蛋白质结构完整性和特异性以及高热力学稳定性。在脓毒症和肺炎模型中，用NE佐剂配制的2C - 葡萄球菌诱导的存活率高于2C - 葡萄球菌/MF59疫苗。此外，在脓毒症模型中，肌肉注射2C - 葡萄球菌/NE产生了保护效果，而鼻内接种途径在肺炎模型中诱导了强大的保护作用。鼻内接种2C - 葡萄球菌/NE在支气管肺泡灌洗液（BALF）中诱导了强烈的黏膜反应，伴有高水平的IgA和IL - 17A，且BALF中的IgG水平与肌肉注射接种途径诱导的水平相当。此外，鼻内给药诱导的血清和BALF对显示出强大的调理吞噬活性。并且，细胞因子中和试验表明IL - 17A在肺炎模型中发挥了保护作用。综上所述，我们的结果表明，鼻内给予用NE佐剂配制的2C - 葡萄球菌在小鼠肺炎模型中产生了理想的保护作用。

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