PDF(Pubmed)
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.
Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. Salmonella enterica serovar Typhimurium (S. Typhimurium), as a bacterium that is easy to engineer and has both adjuvant efficacy and immune stimulation capacity, has become the preferred bacterial vector for purifying OMVs after Escherichia coli. This study focuses on the design of Helicobacter pylori ;(H. pylori) vaccines, utilizing genetically modified Salmonella OMVs to present several major antigens of H. pylori, including UreB, VacA and CagA. The optimal Salmonella OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of H. pylori vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.
Outer membrane vesicles (OMVs), as a novel antigen delivery platform, has been used in vaccine design for various pathogens and even tumors. Salmonella enterica serovar Typhimurium (S. Typhimurium), as a bacterium that is easy to engineer and has both adjuvant efficacy and immune stimulation capacity, has become the preferred bacterial vector for purifying OMVs after Escherichia coli. This study focuses on the design of Helicobacter pylori ;(H. pylori) vaccines, utilizing genetically modified Salmonella OMVs to present several major antigens of H. pylori, including UreB, VacA and CagA. The optimal Salmonella OMV delivery vector and antigen combinations are screened and identified, providing new ideas for the development of H. pylori vaccines and an integrated antigen delivery platform for other difficult to develop vaccines for bacteria, viruses, and even tumors.
摘要：
幽门螺杆菌引起全球流行的感染，与慢性胃炎甚至胃癌的发展高度相关。随着抗生素耐药性的增加,科学家们已经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,虽然目前的策略更喜欢用单一的幽门螺杆菌抗原配制疫苗，他们的潜力尚未充分发挥。外膜囊泡(OMV)是潜在的平台,因为它们可以递送多种抗原。在这项研究中,我们设计了三种关键的幽门螺杆菌抗原蛋白(UreB，卡加,和VacA）到源自鼠伤寒沙门氏菌的OMV表面（S.使用血红蛋白蛋白酶（Hbp）自转运蛋白系统的鼠伤寒）突变菌株。在各种淘汰赛策略中，我们发现，从ΔrfbPΔfliCΔfljBΔompA突变体中分离出的OMV可以引起免疫球蛋白G（IgG）和A（IgA）水平的明显增加，并有效地触发T辅助细胞1-和17-偏向的细胞免疫反应，在预防幽门螺杆菌方面发挥着至关重要的作用。接下来,衍生自ΔrfbPΔfliCΔfljBΔompA突变体的OMV用作载体以递送幽门螺杆菌抗原的不同组合。小鼠模型中的抗体和细胞因子水平以及攻击实验表明,共同递送UreB和CagA可以保护免受幽门螺杆菌和抗原特异性T细胞应答。总之,从鼠伤寒沙门氏菌ΔrfbPΔfliCΔfljBΔompA突变株作为载体，同时使用Hbp自转运蛋白系统导入幽门螺杆菌UreB和CagA作为抗原蛋白，将大大有利于控制幽门螺杆菌感染。
外膜囊泡（OMV），作为一种新型的抗原递送平台，已用于各种病原体甚至肿瘤的疫苗设计。肠病沙门氏菌（S.鼠伤寒)，作为一种易于工程化并具有佐剂功效和免疫刺激能力的细菌，已成为继大肠杆菌之后纯化OMV的首选细菌载体。本研究的重点是幽门螺杆菌的设计；(H.幽门螺杆菌)疫苗，利用基因修饰的沙门氏菌OMV呈递幽门螺杆菌的几种主要抗原，包括UreB,VacA和CagA.筛选并鉴定了最佳的沙门氏菌OMV递送载体和抗原组合，为H.pylori疫苗的开发提供了新的思路，并为其他难以开发的细菌疫苗提供了一个集成的抗原递送平台，病毒,甚至肿瘤。
外膜囊泡（OMV），作为一种新型的抗原递送平台，已用于各种病原体甚至肿瘤的疫苗设计。肠病沙门氏菌（S.鼠伤寒)，作为一种易于工程化并具有佐剂功效和免疫刺激能力的细菌，已成为继大肠杆菌之后纯化OMV的首选细菌载体。本研究的重点是幽门螺杆菌的设计；(H.幽门螺杆菌)疫苗，利用基因修饰的沙门氏菌OMV呈递幽门螺杆菌的几种主要抗原，包括UreB,VacA和CagA.筛选并鉴定了最佳的沙门氏菌OMV递送载体和抗原组合，为H.pylori疫苗的开发提供了新的思路，并为其他难以开发的细菌疫苗提供了一个集成的抗原递送平台，病毒,甚至肿瘤。
