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迈向开发肺炎克雷伯菌疫苗的进展。

Progress towards the development of Klebsiella vaccines.

机构信息

a Center for Vaccine Development and Global Health, University of Maryland School of Medicine , Baltimore , MD , USA.

出版信息

Expert Rev Vaccines. 2019 Jul;18(7):681-691. doi: 10.1080/14760584.2019.1635460. Epub 2019 Jun 28.

Abstract

: Klebsiella pneumoniae (KP) are a leading cause of healthcare-associated infections. The dramatic increase in microbial resistance to third-generation cephalosporin and carbapenem 'front line' antimicrobial agents and the paucity of new antimicrobials have left clinicians with few therapeutic options and resulted in increased morbidity and mortality. Vaccines may reduce the incidence of infections thereby reducing the necessity for antimicrobials and are not subject to antimicrobial resistance mechanisms. : We review whole cell, subunit, capsular polysaccharide (CPS), O polysaccharide (OPS) and conjugate vaccines against KP infection, as well as alternative KP vaccine platforms. : Vaccine-induced antibodies to KP CPS have been protective in preclinical studies, but the number of CPS types (>77) makes vaccines against this virulence factor less feasible. Since four OPS serotypes account of ~80% of invasive KP infections and anti-OPS antibodies are also protective in preclinical studies, both OPS-based conjugate and multiple antigen presenting system (MAPS) vaccines are in active development. Vaccines based on other KP virulence factors, such as outer membrane proteins, type 3 fimbriae (MrkA) and siderophores are at earlier stages of development. Novel strategies for the clinical testing of KP vaccines need to be developed.

摘要

肺炎克雷伯菌(KP)是导致医疗保健相关感染的主要原因。微生物对第三代头孢菌素和碳青霉烯类“一线”抗菌药物的耐药性急剧增加,而新抗菌药物的匮乏,使得临床医生的治疗选择有限,导致发病率和死亡率上升。疫苗可以降低感染的发生率,从而减少对抗菌药物的需求,并且不受抗菌药物耐药机制的影响。

我们综述了针对肺炎克雷伯菌感染的全细胞、亚单位、荚膜多糖(CPS)、O 多糖(OPS)和结合疫苗,以及其他肺炎克雷伯菌疫苗平台。

疫苗诱导的针对肺炎克雷伯菌 CPS 的抗体在临床前研究中具有保护作用,但 CPS 类型数量众多(>77 种),使得针对这种毒力因子的疫苗不太可行。由于四种 OPS 血清型占侵袭性肺炎克雷伯菌感染的~80%,并且抗-OPS 抗体在临床前研究中也具有保护作用,因此基于 OPS 的结合疫苗和多种抗原呈递系统(MAPS)疫苗正在积极开发中。基于其他肺炎克雷伯菌毒力因子的疫苗,如外膜蛋白、III 型菌毛(MrkA)和铁载体,处于早期开发阶段。需要开发用于肺炎克雷伯菌疫苗临床测试的新策略。

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