Outer membrane vesicles from genetically engineered Salmonella enterica serovar Typhimurium presenting Helicobacter pylori antigens UreB and CagA induce protection against Helicobacter pylori infection in mice.

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY Virulence Pub Date : 2024-12-01 Epub Date: 2024-06-27 DOI:10.1080/21505594.2024.2367783
Qiong Liu, Yinpan Shang, Lu Shen, Xiaomin Yu, Yanli Cao, Lingbing Zeng, Hanchi Zhang, Zirong Rao, Yi Li, Ziwei Tao, Zhili Liu, Xiaotian Huang
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Abstract

Helicobacter pylori causes globally prevalent infections that are highly related to chronic gastritis and even development of gastric carcinomas. With the increase of antibiotic resistance, scientists have begun to search for better vaccine design strategies to eradicate H. pylori colonization. However, while current strategies prefer to formulate vaccines with a single H. pylori antigen, their potential has not yet been fully realized. Outer membrane vesicles (OMVs) are a potential platform since they could deliver multiple antigens. In this study, we engineered three crucial H. pylori antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the ΔrfbP ΔfliC ΔfljB ΔompA mutants could cause distinct increases in immunoglobulin G (IgG) and A (IgA) levels and effectively trigger T helper 1- and 17-biased cellular immune responses, which perform a vital role in protecting against H. pylori. Next, OMVs derived from ΔrfbP ΔfliC ΔfljB ΔompA mutants were used as a vector to deliver different combinations of H. pylori antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against H. pylori and antigen-specific T cell responses. In summary, OMVs derived from the S. Typhimurium ΔrfbP ΔfliC ΔfljB ΔompA mutant strain as the vector while importing H. pylori UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling H. pylori infection.

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呈现幽门螺旋杆菌抗原 UreB 和 CagA 的基因工程鼠伤寒沙门氏菌的外膜囊泡可诱导小鼠产生抗幽门螺旋杆菌感染的保护作用。
幽门螺杆菌是全球流行的感染病菌,与慢性胃炎甚至胃癌的发生密切相关。随着抗生素耐药性的增加,科学家们开始寻找更好的疫苗设计策略来根除幽门螺杆菌定植。然而,尽管目前的策略倾向于用单一幽门螺杆菌抗原配制疫苗,但其潜力尚未得到充分发挥。外膜囊泡 (OMV) 是一个潜在的平台,因为它们可以传递多种抗原。在这项研究中,我们利用血红蛋白蛋白酶(Hbp)自动转运系统,将三种关键的幽门螺杆菌抗原蛋白(UreB、CagA 和 VacA)设计到了来自鼠伤寒沙门氏菌(S. Typhimurium)突变株的 OMVs 表面。在各种基因敲除策略中,我们发现从ΔrfbP ΔfliC ΔfljB ΔompA 突变体中分离出的 OMVs 能引起免疫球蛋白 G(IgG)和 A(IgA)水平的明显升高,并能有效触发以 T 辅助细胞 1 和 17 为基础的细胞免疫反应,而这些细胞免疫反应在抵御幽门螺杆菌方面发挥着重要作用。接下来,由 ΔrfbP ΔfliC ΔfljB ΔompA 突变体衍生的 OMVs 被用作载体来传递不同的幽门螺杆菌抗原组合。小鼠模型的抗体和细胞因子水平以及挑战实验表明,联合递送 UreB 和 CagA 可保护幽门螺杆菌和抗原特异性 T 细胞反应。总之,以S. Typhimurium ΔrfbP ΔfliC ΔfljB ΔompA 突变株为载体衍生的OMV,同时利用Hbp自转运系统导入幽门螺杆菌抗原蛋白UreB和CagA,将大大有利于控制幽门螺杆菌感染。
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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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