在小鼠模型中使用含有布鲁氏菌重组触发因子/Bp26/Omp31嵌合蛋白的niosome和甘露糖化niosome进行鼻内和腹膜内免疫以预防布鲁氏菌感染。

IF 2.1 Q4 IMMUNOLOGY Clinical and Experimental Vaccine Research Pub Date : 2024-07-01 Epub Date: 2024-07-31 DOI:10.7774/cevr.2024.13.3.232
Fahimeh Sharif, Razieh Nazari, Mahdi Fasihi-Ramandi, Ramezan Ali Taheri, Mohsen Zargar
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引用次数: 0

摘要

目的:布鲁氏菌病是一种人畜共患病,是影响动物和人类健康的世界性问题。没有有效的人类疫苗以及使用动物疫苗引起的并发症是阻碍在全球根除该疾病的因素之一。然而,生物工程技术已为设计新型靶向高效疫苗铺平了道路。材料与方法:rTBO 作为嵌合抗原(Ag)在大肠杆菌 BL21(DE3)中表达,纯化后载入甘露糖苷化的 niosome。对纳米颗粒的特性进行了评估。使用 rTBO、niosome 和甘露糖化 niosome-rTBO 通过鼻内和腹腔途径对小鼠进行免疫。对免疫小鼠的血清抗体(免疫球蛋白 [Ig]A、IgG、IgG1 和 IgG2a)和脾细胞细胞因子(γ 干扰素、白细胞介素 [IL]-4 和 IL-12)进行了评估。最后,免疫小鼠接受了梅毒杆菌和鲍曼不动杆菌的挑战。与对照组相比,免疫 10、24 和 38 天后,niosomal 抗原(Nio-Ag)和甘露糖化niosomal 抗原(Nio-Man-Ag)产生的抗体水平较高。腹腔注射和鼻内注射Nio-Man-Ag的IgG2a/IgG1滴度比分别为1.2和1.1,而游离Ag和Nio-Ag的IgG2a/IgG1滴度比低于1。与阴性对照组相比,Ag-负载纳米颗粒免疫动物的细胞因子产生量明显较高(pResults:甘露糖基化的noisome和rTBO嵌合蛋白可刺激细胞和体液免疫反应,并产生细胞因子,在布鲁氏菌感染模型中发挥保护性获得性免疫反应的作用。此外,腹腔注射比鼻内注射更能成功提高细胞因子的产生:结论:选择合适的纳米生物体制剂作为免疫佐剂,重组蛋白作为免疫反应刺激剂,可以设计出有效的布鲁氏菌候选疫苗,选择性地诱导细胞和体液免疫反应。
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Intranasal and intraperitoneal immunization against Brucella infection using niosome and mannosylated niosomes containing Brucella recombinant trigger factor/Bp26/Omp31 chimeric protein in a mouse model.

Purpose: Brucellosis, a zoonotic infectious disease, is a worldwide health issue affecting animals and humans. No effective human vaccine and the complications caused by the use of animal vaccines are among the factors that have prevented the eradication of the disease worldwide. However, bio-engineering technologies have paved the way for designing new targeted and highly efficacious vaccines. In this regard, the study aimed to evaluate immunity induced by mannosylated niosome containing Brucella recombinant trigger factor/Bp26/Omp31 (rTBO) chimeric protein in a mouse model.

Materials and methods: rTBO as chimeric antigen (Ag) was expressed in Escherichia coli BL21 (DE3) and, after purification, loaded on niosome and mannosylated niosome. The characteristics of the nanoparticles were assessed. The mice were immunized using rTBO, niosome, and mannosylated niosome-rTBO in intranasal and intraperitoneal routes. Serum antibodies (immunoglobulin [Ig]A, IgG, IgG1, and IgG2a) and splenocyte cytokines (interferon-gamma, interleukin [IL]-4, and IL-12) were evaluated in immunized mice. Finally, immunized mice were challenged by B. melitensis and B. abortus. A high antibody level was produced by niosomal antigen (Nio-Ag) and mannosylated noisomal antigen (Nio-Man-Ag) compared to the control after 10, 24, and 38 days of immunization. The IgG2a/IgG1 titer ratio for Nio-Man-Ag was 1.2 and 1.1 in intraperitoneal and intranasal methods and lower than one in free Ag and Nio-Ag. Cytokine production was significantly higher in the immunized animal with Ag-loaded nanoparticles than in the negative control group (p<0.05). Moreover, cytokine and antibody levels were significantly higher in the injection than in the inhalation method (p<0.05).

Results: The combination of mannosylated noisome and rTBO chimeric proteins stimulate the cellular and humoral immune response and produce cytokines, playing a role in developing the protective acquired immune response in the Brucella infectious model. Also, the intraperitoneal route resulted in a successful enhancement of cytokines production more than intranasal administration.

Conclusion: Designing an effective vaccine candidate against Brucella that selectively induces cellular and humoral immune response can be done by selecting a suitable nanoniosome formulation as an immunoadjuvant and recombinant protein as an immune response-stimulating Ag.

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来源期刊
CiteScore
3.70
自引率
3.70%
发文量
29
审稿时长
8 weeks
期刊介绍: Clin Exp Vaccine Res, the official English journal of the Korean Vaccine Society, is an international, peer reviewed, and open-access journal. It covers all areas related to vaccines and vaccination. Clin Exp Vaccine Res publishes editorials, review articles, special articles, original articles, case reports, brief communications, and correspondences covering a wide range of clinical and experimental subjects including vaccines and vaccination for human and animals against infectious diseases caused by viruses, bacteria, parasites and tumor. The scope of the journal is to disseminate information that may contribute to elaborate vaccine development and vaccination strategies targeting infectious diseases and tumors in human and animals. Relevant topics range from experimental approaches to (pre)clinical trials for the vaccine research based on, but not limited to, basic laboratory, translational, and (pre)clinical investigations, epidemiology of infectious diseases and progression of all aspects in the health related issues. It is published printed and open accessed online issues (https://ecevr.org) two times per year in 31 January and 31 July. Clin Exp Vaccine Res is linked to many international databases and is made freely available to institutions and individuals worldwide
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