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不同方法制备外膜囊泡疫苗的研究进展:制备方法对保护效力的影响。

Development of Different Methods for Preparing Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy.

机构信息

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

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.

出版信息

Front Immunol. 2020 Jun 23;11:1069. doi: 10.3389/fimmu.2020.01069. eCollection 2020.

DOI:10.3389/fimmu.2020.01069
PMID:32655550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7324643/
Abstract

() is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against infection.

摘要

由于出现了多药耐药或泛耐药菌株,()正成为一个普遍的全球关注问题。通过开发针对耐药病原体的疫苗来应对抗微生物药物耐药性问题,正在成为一种常见策略。在这项研究中,开发了不同的方法来制备外膜囊泡(AbOMV)疫苗。sOMV(自发释放的 AbOMV)从培养上清液中提取,而 SuOMV(蔗糖提取的 AbOMV)和 nOMV(天然 AbOMV)则从细菌细胞中制备。三种 AbOMV 在产量、粒径、蛋白组成和 LPS/DNA 含量方面表现出显著差异。为了比较三种 AbOMV 的保护效力,将各组小鼠分别通过肌肉内或鼻内免疫接种每种 AbOMV。两种途径的接种均能显著抵抗致死性和亚致死性 挑战。此外,鼻内接种提供了更强大的保护,这可能归因于在黏膜部位诱导了显著的 sIgA 反应。在三种 AbOMV 中,SuOMV 无论是肌肉内还是鼻内免疫接种,都能引发针对 感染的最高水平的保护免疫,其特征是表达最深刻的特异性血清 IgG 或黏膜 sIgA。总之,制备方法对 AbOMV 的产量、形态和组成有显著影响,进而影响对 感染的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ae/7324643/1ae2adb04b2a/fimmu-11-01069-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ae/7324643/5205d91432be/fimmu-11-01069-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ae/7324643/8e571046f6c5/fimmu-11-01069-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ae/7324643/5b9dc6fa5624/fimmu-11-01069-g0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ae/7324643/1ae2adb04b2a/fimmu-11-01069-g0007.jpg

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