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针对……的免疫反应及向治疗的转化

Immune response against and translation to therapy.

作者信息

Sehgal Kanika, Khanna Sahil

机构信息

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

出版信息

Therap Adv Gastroenterol. 2021 May 7;14:17562848211014817. doi: 10.1177/17562848211014817. eCollection 2021.

Abstract

The pathogenesis of infection (CDI) has largely been attributed to the action of two major toxins - A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection.

摘要

艰难梭菌感染(CDI)的发病机制很大程度上归因于两种主要毒素——毒素A和毒素B的作用。已证明针对这些毒素增强的全身体液免疫反应对复发性CDI具有保护作用。多年来,人们开发了针对这两种毒素的全人源单克隆抗体,以应对复发性CDI发病率不断上升的情况。为评估抗毒素A单克隆抗体actoxumab和抗毒素B单克隆抗体bezlotoxumab的疗效而进行的临床试验表明,bezlotoxumab可显著降低复发性感染率,而actoxumab则无此效果。在至少有一项复发高危因素的患者中,包括年龄≥65岁、免疫功能低下状态、既往CDI和严重CDI患者,观察到了显著的治疗益处。鉴于毒素A和毒素B具有免疫原性,目前正在进行疫苗试验,旨在预防初次感染。

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