Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients.
Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients.
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DOI：
10.1128/msphere.01335-20
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发表时间：
2021-03-03
期刊：
影响因子：
4.8
通讯作者：
Fries BC
中科院分区：
文献类型：
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作者：
Banerjee K;Motley MP;Diago-Navarro E;Fries BC
在开发基于荚膜多糖（CPS）的疫苗时，必须考虑耐碳青霉烯类肺炎克雷伯菌（CR-Kp）菌株序列258型（ST 258）内的CPS异质性。在这里，我们试图表征由CR-Kp感染的患者引起的CPS特异性抗体应答。从33名CR-Kp培养阳性的医院患者中收集血浆和细菌分离株。通过wzi测序对分离物胶囊进行分型。针对3种流行的CR-Kp CPS类型（wzi 29、wzi 154和wzi 50）研究了患者抗体的反应性和疗效测量。在79%的感染患者中记录了针对wzi 154和wzi 50 CPS的高IgG滴度。患者衍生（PD）IgG凝集CR-Kp和限制生长优于幼稚IgG，并促进从其供体分离的血清型菌株的吞噬作用。此外，来自wzi 50和wzi 154患者的聚IgG促进了对不一致CR-Kp血清型的吞噬作用。当聚IgG耗尽CPS特异性IgG时，这种作用丧失。此外，用wzi 50患者来源的IgG预调理的wzi 50、wzi 154和wzi 29 CR-Kp菌株感染的小鼠表现出比对照更低的肺CFU。在wzi 50和wzi 154感染中，wzi 50抗体（Ab）的耗尽逆转了这种效应，而wzi 154 Ab耗尽降低了针对wzi 29 CR-Kp的聚IgG效力。我们是第一个通过体外和体内模型报告来自CR-Kp患者的CPS特异性Ab的交叉反应特性的人。耐碳青霉烯类肺炎克雷伯菌是一种迅速出现的公共卫生威胁，可导致高达50%的受影响患者发生致命感染。由于其对几乎所有抗菌药物的耐药性，迫切需要开发替代疗法，如抗体和疫苗。荚膜多糖是重要的靶点，因为它们对肺炎克雷伯氏菌的发病至关重要。荚膜多糖是非常多样化的，因此，研究宿主的荚膜型特异性抗体对于开发有效的抗CPS免疫疗法至关重要。在这项研究中，我们是第一个描述感染患者对表达不同wzi荚膜类型的碳青霉烯类耐药肺炎克雷伯菌的体液反应的人。本研究首次报告了CPS特异性抗体在体外和体内模型中交叉反应特性的功效。
Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.