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针对艰难梭菌的免疫策略。

Immunization Strategies Against Clostridioides difficile.

机构信息

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.

CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1111, CNRS UMR5308, ENS Lyon, Lyon, France.

出版信息

Adv Exp Med Biol. 2024;1435:117-150. doi: 10.1007/978-3-031-42108-2_7.

DOI:10.1007/978-3-031-42108-2_7
PMID:38175474
Abstract

Clostridioides difficile (C. difficile) infection (CDI) is an important healthcare but also a community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients, and to prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to elicit immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile, and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product, and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins, and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens and either toxins or colonization factors.

摘要

艰难梭菌(C. difficile)感染(CDI)是一种重要的医疗保健相关疾病,也是一种社区相关性疾病。CDI 被认为是一种公共卫生威胁和经济负担。一个主要问题是复发率很高。除了经典的抗生素治疗外,还需要新的治疗策略来预防感染、治疗患者和预防复发。虽然粪便移植已被推荐用于治疗复发,但另一个关键方法是引发针对艰难梭菌及其毒力因子的免疫。在这里,在总结了艰难梭菌的毒力因子、宿主对艰难梭菌的免疫反应及其在疾病结果中的作用之后,我们回顾了针对 CDI 开发的被动免疫疗法和疫苗的不同方法。被动免疫策略是根据靶抗原、基于抗体的产品及其给药途径设计的。同样,对于主动免疫策略,疫苗抗原可以针对毒素或表面蛋白,并且可以通过肠外或粘膜途径进行免疫接种。对于被动免疫和疫苗接种,我们首先介绍了在动物模型中进行的免疫测定,然后介绍了在人类和相关临床试验中的免疫测定。根据给药方式(肠外或粘膜)和靶抗原(毒素或定植因子),对不同的研究进行了介绍。

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