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生产高产量细菌仿生囊泡以诱导黏膜免疫抵抗禽致病性 。

Development of High-Production Bacterial Biomimetic Vesicles for Inducing Mucosal Immunity Against Avian Pathogenic .

机构信息

College of Veterinary Medicine, Yangzhou University, Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2024 Nov 9;25(22):12055. doi: 10.3390/ijms252212055.

Abstract

To evaluate the immunoprotective effect of bacterial biomimetic vesicles (BBVs) against avian pathogenic (APEC), a Δ J11 mutant strain was generated by deleting the gene in the low pathogenic O78 serotype J11 strain. The total protein content of outer membrane vesicles (OMVs) derived from the Δ J11 strain exhibited a sevenfold increase compared to the wild-type strain. Additionally, high-pressure homogenization technology was employed to produce BBVs, resulting in a sixfold increase in total protein content compared to spontaneously secreted OMVs from Δ J11. The immunogenicity of both OMVs and BBVs was assessed through intranasal or intramuscular immunization in specific pathogen-free (SPF) chickens. Results demonstrated that intranasal immunization with OMVs or BBVs in chickens elicited specific IgY antibodies against APEC outer membrane proteins and specific sIgA antibodies in the nasal cavity and trachea, as well as a significant increase in the proliferation response of chicken peripheral blood lymphocytes. The bacterial load in the blood and various organs of the challenged chickens were significantly reduced, resulting in a 66.67% and 58.30% survival rate against a high pathogenic serotype O78 strain challenge, while the control group exhibited only a 16.67% survival rate. The intramuscular immunization with OMVs or BBVs in chickens only induced specific IgY antibodies, with a survival rate of only 33.33% for challenged chickens during the same period. Therefore, intranasal vaccination of the highly productive BBVs is capable of eliciting an immune response similar to that of OMVs and providing protection against APEC infection, thus offering innovative insights for the advancement of APEC vaccines.

摘要

为了评估细菌仿生囊泡(BBVs)对禽致病性大肠杆菌(APEC)的免疫保护作用,通过缺失低致病性 O78 血清型 J11 株中的基因,生成了ΔJ11 突变株。与野生型菌株相比,ΔJ11 菌株来源的外膜囊泡(OMVs)的总蛋白含量增加了七倍。此外,采用高压匀浆技术制备 BBVs,与ΔJ11 自发分泌的 OMVs 相比,总蛋白含量增加了六倍。通过 SPF 鸡的鼻腔或肌肉内免疫评估了 OMVs 和 BBVs 的免疫原性。结果表明,鼻腔内免疫 OMVs 或 BBVs 可在鸡中诱导针对 APEC 外膜蛋白的特异性 IgY 抗体和鼻腔及气管中的特异性 sIgA 抗体,以及鸡外周血淋巴细胞增殖反应显著增加。攻毒鸡血液和各器官中的细菌载量明显降低,对高致病性血清型 O78 株攻毒的存活率分别为 66.67%和 58.30%,而对照组的存活率仅为 16.67%。同期鸡肌肉内免疫 OMVs 或 BBVs 仅诱导特异性 IgY 抗体,攻毒鸡的存活率仅为 33.33%。因此,高产量的 BBVs 鼻腔接种可引起类似于 OMVs 的免疫反应,并提供针对 APEC 感染的保护,为 APEC 疫苗的研发提供了创新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd84/11593933/5662314175ff/ijms-25-12055-g001.jpg

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