Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates

Klaus Panthel; Wolfgang Jechlinger; Alexander Matis; Manfred Rohde; Michael Szostak; Werner Lubitz; Rainer Haas

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Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates

机译：通过PhiX蛋白E介导的灭活产生幽门螺杆菌幽灵及其作为疫苗候选者的评估

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Bacterial ghosts are empty cell envelopes, which may be generated by the controlled expression of the PhiX174 lysis gene E in gram-negative bacteria to obtain vaccine candidates. We describe here the application of this technology to Helicobacter pylori. The lysis gene cassette was cloned into an Escherichia coli-Helicobacter pylori shuttle vector and introduced into an H. pylori recipient strain by bacterial conjugation. Temperature induction of the lysis gene cassette revealed a quantitative killing of the H. pylori culture without induction of lysis-resistant bacteria. Biochemical and transmission electron microscopic studies identified structurally intact H. pylori. Prophylactic oral vaccination experiments using these H. pylori ghosts in the BALB/c mouse model showed a significant reduction of the bacterial load in the ghost group, as measured by a quantitative bacterial reisolation procedure. Ten of 10 and 5 of 10 mice were protected, respectively, without the use of a mucosal adjuvant. Coadministration of ghosts with cholera toxin as mucosal adjuvant resulted in a complete protection of 10 of 10 and 8 of 8 mice against H. pylori challenge, with three animals showing a sterile immunity.

机译：细菌鬼魂是空细胞被膜，它可能是由革兰氏阴性菌中PhiX174裂解基因 E 的受控表达产生的，从而获得了候选疫苗。我们在这里描述了这项技术在幽门螺杆菌中的应用。将裂解基因盒克隆到大肠杆菌-幽门螺旋杆菌穿梭载体中，并导入 H。细菌结合产生幽门螺旋杆菌受体菌株。裂解基因盒的温度诱导显示定量杀死 H。无需诱导抗裂解细菌的幽门螺杆菌培养。生化和透射电子显微镜研究确定了结构完整的 H。使用这些 H进行预防性口服疫苗接种的实验。通过定量细菌再分离程序测量，BALB / c小鼠模型中的幽门螺杆菌幽灵显示出幽灵组中细菌载量的显着降低。在不使用粘膜佐剂的情况下分别保护了10只小鼠中的10只和10只小鼠中的5只。幽灵与霍乱毒素作为粘膜佐剂的共同给药导致对10只小鼠中的10只和8只小鼠中的8只针对 H的完全保护。幽门螺杆菌攻击，三只动物表现出无菌免疫力。 展开▼

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《Infection and immunity》 |2003年第1期|共8页

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Klaus Panthel; Wolfgang Jechlinger; Alexander Matis; Manfred Rohde; Michael Szostak; Werner Lubitz; Rainer Haas;
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中图分类医学免疫学;

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专利

1. Generation of Biotechnology-Derived Flavobacterium columnare Ghosts by PhiX174 Gene E-Mediated Inactivation and the Potential as Vaccine Candidates against Infection in Grass Carp [J] . Wenxing Zhu, Guiwen Yang, Yuyu Zhang, Journal of biomedicine & biotechnology . 2012,第6期

机译：通过PhiX174基因E介导的失活产生生物技术衍生的黄杆菌幽灵，并具有抗草鱼感染的疫苗候选能力。

2. Generation and immunity effect evaluation of biotechnology-derived Aeromonas veronii ghost by PhiX174 gene E-mediated inactivation in koi (Cyprinus carprio koi) [J] . Jiang Na, Luo Lin, Xing Wei, Fish & Shellfish Immunology . 2019,第期

机译：PHIX174基因E介导的KOI（Cyprinus carprio Koi）的生物技术衍生Aeromonas Veronii Ghost的生成和免疫效应评估

3. Generation of Biotechnology-DerivedFlavobacterium columnareGhosts by PhiX174 GeneE-Mediated Inactivation and the Potential as Vaccine Candidates against Infection in Grass Carp [J] . WenxingZhu, GuiwenYang, YuyuZhang, BioMed research international . 2012,第5期

机译：通过PhiX174 GeneE介导的失活产生生物技术衍生的黄杆菌GhostesGhosts以及抗草鱼感染的疫苗候选疫苗的潜力

4. In vitro studies of chlorin e6-assisted photodynamic inactivation of Helicobacter pylori [C] . C. Simon, C. Mohrbacher, D. Huettenberger, Optical methods for tumor treatment and detection: mechanisms and techniques in photodynamic therapy XXIII . 2014

机译：二氢卟酚e6辅助的幽门螺杆菌光动力学灭活的体外研究

5. Biophysical characterization and stabilization of recombinant protein subunit vaccine candidates against Shigella flexneri and Helicobacter pylori [D] . Choudhari, Shyamal Pralhad 2014

机译：抗弗氏志贺氏菌和幽门螺杆菌的重组蛋白亚基疫苗候选物的生物物理特性和稳定性

6. Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates [O] . Klaus Panthel, Wolfgang Jechlinger, Alexander Matis, 2003

机译：通过PhiX蛋白E介导的灭活产生幽门螺杆菌幽灵及其作为疫苗候选者的评估

7. Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates [O] . Panthel, Klaus, Jechlinger, Wolfgang, Matis, Alexander, 2003

机译：通过PhiX蛋白E介导的灭活产生幽门螺杆菌幽灵及其作为疫苗候选者的评估

1. 基于PhiX174基因E介导的遗传灭活多杀性巴氏杆菌 [J] . 朱必凤 ,杨旭夫 ,刘东胜 . 南昌大学学报（理科版） . 2012,第006期

2. 幽门螺杆菌cagA蛋白及其疫苗侯选抗原对T细胞Fas Ligand介导凋亡的调节作用 [J] . 王继德 ,陈烨 ,赖卓胜 . 中华医学杂志 . 2000,第011期

3. 最新种猪口蹄疫型灭活疫苗及型-型二价灭活疫苗免疫效果评估 [J] . 刘针伶 ,黄溢泓 ,全琛宇 . 养殖与饲料 . 2020,第006期

4. PRRSV-VR2332减毒活疫苗不影响猪瘟疫苗和猪圆环病毒2型灭活疫苗诱导的抗体产生 [J] . 李洋 ,高胜 ,焦点 . 畜牧兽医学报 . 2021,第011期

5. 猪瘟活疫苗、猪圆环病毒2型基因工程疫苗和猪肺炎支原体灭活疫苗三种疫苗联合免疫效果的评估 [J] . 张召 ,马红伟 ,魏烨 . 郑州牧业工程高等专科学校学报 . 2021,第001期

6. 猪瘟病毒E2蛋白重组杆状病毒灭活疫苗与猪瘟活疫苗的免疫效力比较研究 [C] . Junhui Li ,李俊辉 ,Zunbao Wang . 2017猪瘟防控技术研讨会 . 2017

7. 基于PhiX174基因E介导的副猪嗜血杆菌细菌幽灵研究 [A] . 王敏 . 2007

1. 抗phiX174噬菌体裂解蛋白E的单克隆抗体、产生该抗体的杂交瘤细胞株及其表位 [P] . 中国专利： CN102558346B . 2013.12.18

2. 抗phiX174噬菌体裂解蛋白E的单克隆抗体、产生该抗体的杂交瘤细胞株及其表位 [P] . 中国专利： CN102558346A . 2012-07-11

3. Vaccine composition, use of a helicobacter pylori polypeptide flge or a modified form thereof, use of the same, vaccine composition to induce a protective immune response to helicobacter pylori infection, in vitro diagnostic process of helicobacter pylori infection, kit method for detecting helicobacter pylori infection in a mammal including man, and process for eliciting a protective immune response against helicobacter pylori infection in a mammal [P] . 外国专利： BR9810026A . 2000-09-19

机译：疫苗组合物，幽门螺杆菌多肽壁或其修饰形式的用途，其用途，疫苗组合物诱导对幽门螺杆菌感染的保护性免疫应答，幽门螺杆菌感染的体外诊断方法，用于检测幽门螺杆菌感染的试剂盒方法包括人在内的哺乳动物中的表达，以及引起针对幽门螺杆菌感染的保护性免疫应答的方法

4. ‡ nucleic acid, nucleic acid molecule, probe, recombinant expression vector, cell, processes to produce a h polypeptide. pylori and to detect the presence of a helicobacter pylori nucleic acid in a sample, h. pylori isolated, cell, cellular and secreted envelope polypeptides from h. pylori or its fragments, fusion protein, vaccine formulation for the prophylaxis or treatment of an infection by h. pylori, and, processes to treat or reduce a risk of infection by h. pylori in a subject and to produce a vaccine formulation. [P] . 外国专利： BR9712587A . 1999-10-26

机译：‡核酸，核酸分子，探针，重组表达载体，细胞，产生h多肽的过程。并检测样品中是否存在幽门螺杆菌核酸; h。来自h的幽门螺杆菌分离的，细胞，细胞和分泌的包膜多肽幽门螺杆菌或其片段，融合蛋白，疫苗制剂，用于预防或治疗h感染。幽门螺杆菌，以及治疗或降低h感染风险的方法。幽门螺杆菌在受试者体内并产生疫苗制剂。

5. isolated nucleic acid, molecule thereof, probe, recombinant expression vector, cell, polypeptide, fusion protein vaccine formulation and processes for producing a h. pylori, to detect the presence of a helicobacter nucleic acid in a sample, to treat or reduce a risk of infection by h. pylori in an individual and to produce a vaccine formulation [P] . 外国专利： BR9714133A . 2000-02-29

机译：分离的核酸，其分子，探针，重组表达载体，细胞，多肽，融合蛋白疫苗制剂和产生h的方法。幽门螺杆菌，用于检测样品中幽门螺杆菌核酸的存在，以治疗或降低h感染的风险。幽门螺杆菌感染并生产疫苗制剂

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Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates

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