Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia

Brook E. Ragle; Juliane Bubeck Wardenburg

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Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia

机译：抗α-溶血素溶酶单克隆抗体介导针对金黄色葡萄球菌肺炎的保护

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Staphylococcus aureus pneumonia is one of the most common invasive diseases caused by this human pathogen. S. aureus alpha-hemolysin, a pore-forming cytotoxin, is an essential virulence factor in the pathogenesis of pneumonia. Vaccine-based targeting of this toxin provides protection against lethal staphylococcal pneumonia in a murine model system, suggesting that a monoclonal antibody-based therapy may likewise prove to be efficacious for prevention and treatment of this disease. We report the generation of two distinct anti-alpha-hemolysin monoclonal antibodies that antagonize toxin activity, preventing human lung cell injury in vitro and protecting experimental animals against lethal S. aureus pneumonia. Each of these two monoclonal antibodies recognized an epitope within the first 50 amino acid residues of the mature toxin and blocked the formation of a stable alpha-hemolysin oligomer on the target cell surface. Active immunization with the first 50 amino acids of the toxin also conferred protection against S. aureus pneumonia. Together, these data reveal passive and active immunization strategies for prevention or therapy of staphylococcal pneumonia and highlight the potential role that a critical epitope may play in defining human susceptibility to this deadly disease.

机译：金黄色葡萄球菌肺炎是由这种人类病原体引起的最常见的侵袭性疾病之一。 S。 aureus α-溶血素是一种成孔性细胞毒素，是肺炎发病过程中必不可少的毒力因子。在疫苗模型系统中，这种毒素的基于疫苗的靶向作用提供了针对致命性葡萄球菌肺炎的保护作用，这表明基于单克隆抗体的疗法同样可以有效地预防和治疗该疾病。我们报道了两种独特的抗α-溶血素单克隆抗体的产生，它们能拮抗毒素的活性，在体外防止人肺细胞的损伤，并保护实验动物免于致命的 S。金黄色肺炎。这两种单克隆抗体均识别成熟毒素的前50个氨基酸残基内的表位，并阻止在靶细胞表面形成稳定的α-溶血素低聚物。用毒素的前50个氨基酸进行主动免疫还可赋予针对 S的保护。金黄色肺炎。总之，这些数据揭示了预防或治疗葡萄球菌性肺炎的被动和主动免疫策略，并强调了关键表位在定义人类对这种致命疾病的敏感性中可能发挥的潜在作用。 展开▼

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《Infection and immunity》 |2009年第7期|共7页

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Brook E. Ragle; Juliane Bubeck Wardenburg;
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1. Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia [J] . Brook E. Ragle, Juliane Bubeck Wardenburg Infection and immunity . 2009,第7期

机译：抗α-溶血素溶酶单克隆抗体介导针对金黄色葡萄球菌肺炎的保护

2. Characterization of the mechanism of protection mediated by CS-D7, a monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) [J] . Clark Desmond, Cope Leslie PhD, Drummond James PhD, Frontiers in Cellular and Infection Microbiology . 2012,第2012期

机译：表征由金黄色葡萄球菌铁调节的表面决定簇B（IsdB）的单克隆抗体CS-D7介导的保护机制

3. Monoclonal antibody to prevent Staphylococcus aureus pneumonia? [J] . McConnell John The Lancet infectious diseases . 2019,第12期

机译：单克隆抗体预防金黄色葡萄球菌肺炎？

4. STRUCTURAL AND MECHANISTIC BASIS FOR THE O-ACETYLATION OF PEPTIDOGLYCAN BY THE VIRULENCE FACTORS PatB OF Neisseria gonorrhoeae AND OatA FROM BOTH Staphylococcus aureus AND Streptococcus pneumoniae. [C] . Anthony J. Clarke, David Sychantha, Ashley Brott International Carbohydrate Symposium . 2018

机译：肽聚糖的结构和机械基础，肽因子毒力因子刺痛的因子和来自金黄色葡萄球菌的葡萄球菌和肺炎链球菌肺炎链球菌的毒性因子。

5. Part 1. Scope and mechanism of peptide cyclodimerization by the copper(I)-mediated azide-alkyne cycloaddition reaction. Part 2. Controlling Staphylococcus aureus infection by disrupting bacterial communication with a monoclonal antibody [D] . Jagasia, Reshma 2008

机译：第1部分。铜（I）介导的叠氮化物-炔烃环加成反应进行的肽环二聚作用的范围和机理。第2部分。通过破坏与单克隆抗体的细菌传播来控制金黄色葡萄球菌感染

6. Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia [O] . Brook E. Ragle, Juliane Bubeck Wardenburg 2009

机译：抗α-溶血素溶酶单克隆抗体介导针对金黄色葡萄球菌肺炎的保护

7. Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia▿ [O] . Ragle, Brook E., Bubeck Wardenburg, Juliane 2009

机译：抗α-溶血素溶酶单克隆抗体介导针对金黄色葡萄球菌肺炎的保护作用

1. 抗肺炎链球菌溶血素蛋白单克隆抗体的制备及表征 [J] . 王丹丹 ,侯宏嘉 ,卢井才 . 中华微生物学和免疫学杂志 . 2015,第009期

2. 亚抑菌浓度穿心莲提取物对减缓金黄色葡萄球菌α-溶血素介导的A549细胞损伤作用的影响 [J] . 霍明飞 ,王鑫 ,戴小寒 . 中国畜牧兽医 . 2013,第005期

3. 肺炎链球菌溶血素黏膜免疫抗定植保护作用的研究 [J] . 杨晓丹 ,袁军 ,王虹 . 医学分子生物学杂志 . 2011,第001期

4. 087 肺炎球菌表面蛋白A与IL-12鼻腔接种能增强抗肺炎球菌感染的抗体介导性调理作用及保护性免疫 [J] . . 国际生物制品学杂志 . 2002,第005期

5. 牛源抗金黄色葡萄球菌α溶血素单链抗体研制 [J] . 张波 ,王曼 ,王凤青 . 上海交通大学学报（农业科学版） . 2019,第002期

6. 抗金黄色葡萄球菌核酸酶的单克隆抗体--研究核酸酶折叠的有用探针 [C] . 程鹏 . 第八次全国生物化学与分子生物学学术会议 . 1997

7. 溶瘤腺病毒介导抑癌基因HCCS1治疗肿瘤的实验研究；抗膜联蛋白Ⅰ单克隆抗体的制备与鉴定 [A] . 蔡幸 . 2006

1. 一种抗金黄色葡萄球菌α溶血素单克隆抗体及应用 [P] . 中国专利： CN109384844B . 2020.12.18

2. 一种抗金黄色葡萄球菌α溶血素单克隆抗体及应用 [P] . 中国专利： CN109384844A . 2019-02-26

3. Staphylococcus aureus-Specific Novel Monoclonal Antibody Hybridoma For Producing The Antibody Method For Detecting The Same Comprising The Antibody And Kit For Detecting The Same [P] . 外国专利： KR101851332B1 . 2018-04-23

机译：金黄色葡萄球菌特异性新型单克隆抗体杂交瘤，用于生产检测该抗体的方法包括该抗体的试剂盒和用于检测该试剂盒的试剂盒

4. Staphylococcus aureus-Specific Novel Monoclonal Antibody Hybridoma For Producing The Antibody Method For Detecting The Same Comprising The Antibody And Kit For Detecting The Same [P] . 外国专利： KR20180001538A . 2018-01-04

机译：金黄色葡萄球菌特异性新型单克隆抗体杂交瘤，用于生产检测该抗体的方法包括该抗体的试剂盒和用于检测该试剂盒的试剂盒

5. "monoclonal antibody that neutralizes staphylococcus aureus, its medical or diagnostic use, a pharmaceutical or diagnostic preparation, antibody-encoding nucleic acid molecules, and a method for producing the antibody." [P] . 外国专利： BR112017021830A2 . 2018-07-10

机译：“中和金黄色葡萄球菌的单克隆抗体，其医学或诊断用途，药物或诊断制剂，编码抗体的核酸分子以及产生该抗体的方法。”

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Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against Staphylococcus aureus Pneumonia

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