Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses.

Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses.
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DOI:
10.3389/fimmu.2021.705533
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发表时间:
2021
影响因子:
7.3
通讯作者:
Brown J
Brown J
中科院分区:
医学2区
文献类型:
--
作者:
Kamuyu G;Suen Cheng Y;Willcocks S;Kewcharoenwong C;Kiratisin P;Taylor PW;Wren BW;Lertmemongkolchai G;Stabler RA;Brown J

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抗体疗法可能是治疗由多重耐药(MDR)鲍曼不动杆菌引起的感染的一种替代治疗选择。由于鲍曼不动杆菌具有多种荚膜血清型,一种通用的抗体疗法需要针对保守的蛋白质抗原而非荚膜多糖。我们用单一或多种鲍曼不动杆菌菌株免疫小鼠以诱导对蛋白质抗原的抗体反应,然后评估这些反应是否对一组基因多样的临床鲍曼不动杆菌分离株提供交叉保护。免疫后的小鼠产生了对多种蛋白质抗原的抗体反应。流式细胞术IgG结合试验和免疫印迹表明,与单一菌株免疫的小鼠血清相比,用多种菌株免疫的小鼠血清对同源和异源临床菌株的识别能力有所提高。荚膜部分抑制了IgG对细菌的识别以及人类中性粒细胞对吞噬作用的促进。然而,用多种菌株免疫后,针对蛋白质抗原的血清抗体促进了中性粒细胞对异源鲍曼不动杆菌菌株的吞噬作用。在感染模型中,用多种菌株免疫的小鼠在受到异源菌株攻击后,脾脏和肝脏中的细菌数量较低。这些数据表明,针对蛋白质抗原的抗体可以提高对多种鲍曼不动杆菌菌株的免疫识别和保护作用,为其作为一种抗体疗法的应用提供了支持。
Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy.
使用 22 kDa 外膜蛋白进行免疫可引发针对多重耐药鲍曼不动杆菌的保护性免疫。
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