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人类曼氏血吸虫感染新模型可用于药物研发
作者:小柯机器人 发布时间:2020/2/28 13:41:41

荷兰莱顿大学医学中心Meta Roestenberg小组近日取得一项新成果。他们开发出一种可控制的人类曼氏血吸虫感染模型,可用于开发新药、疫苗和诊断方法。相关论文2020年2月17日在线发表于《自然—医学》杂志。

研究人员在荷兰莱顿大学医学中心在17名感染了雄性曼氏血吸虫尾蚴(不产卵)的志愿者中进行了剂量递增的临床安全性试验(clinicaltrials.gov编号:NCT02755324)。主要终点是不良事件和感染性。
 
研究人员发现与急性血吸虫病综合征相关的不良事件的剂量相关增加,这发生在17名志愿者中的9名。总体而言,有5名志愿者(高剂量组中的3名和中剂量组11名中的2名)报告了严重的不良事件。蠕虫来源的循环阳极抗原是主要感染终点的生物标记,在接触后3-10周内82%的志愿者达到峰值。所有志愿者均显示CD4+T细胞产生IgM和IgG1血清转换以及蠕虫特异性细胞因子的产生。
 
暴露后12周,所有志愿者均接受吡喹酮治疗。感染20只曼氏血吸虫尾蚴导致18%的志愿者出现严重不良事件,并且感染率很高。这种感染模型为快速研发治疗和预防血吸虫病药物提供了可能。
 
据介绍,血吸虫病的治疗依赖于单一药物吡喹酮,该药物不足以控制高流行地区的传播。目前迫切需要新型药物和疫苗。实验性的血吸虫病人类模型可以加速这些药物的开发。
 
附:英文原文

Title: A controlled human Schistosoma mansoni infection model to advance novel drugs, vaccines and diagnostics

Author: Marijke C. C. Langenberg, Marie-Astrid Hoogerwerf, Jan Pieter R. Koopman, Jacqueline J. Janse, Janneke Kos-van Oosterhoud, Carola Feijt, Simon P. Jochems, Claudia J. de Dood, Roos van Schuijlenburg, Arifa Ozir-Fazalalikhan, Mikhael D. Manurung, Erliyani Sartono, Martha T. van der Beek, Batrice M. F. Winkel, Petra H. Verbeek-Menken, Koen A. Stam, Fijs W. B. van Leeuwen, Pauline Meij, Angela van Diepen, Lisette van Lieshout, Govert J. van Dam, Paul L. A. M. Corstjens, Cornelis H. Hokke, Maria Yazdanbakhsh, Leo G. Visser, Meta Roestenberg

Issue&Volume: 2020-02-17

Abstract: Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3–10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.

DOI: 10.1038/s41591-020-0759-x

Source: https://www.nature.com/articles/s41591-020-0759-x

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex