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努力研发抗新孢子虫病疫苗和化疗药物——历经坎坷——展望未来。

Working towards the development of vaccines and chemotherapeutics against neosporosis-With all of its ups and downs-Looking ahead.

机构信息

Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

出版信息

Adv Parasitol. 2024;124:91-154. doi: 10.1016/bs.apar.2024.01.001. Epub 2024 Feb 6.

Abstract

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.

摘要

刚地弓形虫是一种顶复门的专性细胞内寄生虫,是导致牛繁殖失败的主要原因,还会影响其他农场动物和家养动物,也会引起所有年龄段犬的神经肌肉疾病。在牛中,新孢子虫病是一个重要的健康问题,具有相当大的经济影响。迄今为止,市场上没有保护性疫苗或化疗药物。免疫预防长期以来被认为是最好的控制措施。参与宿主细胞相互作用和入侵的蛋白以及介导炎症反应的抗原一直是评估疫苗的最常用靶点。然而,尽管付出了相当大的努力,但迄今为止还没有有效的疫苗被引入市场。开发有效的化合物来限制刚地弓形虫速殖子垂直传播的影响,已经成为疫苗接种的替代或补充方法,前提是可以确定合适的靶点以及安全有效的药物。此外,这两种治疗策略的结合可能会很有趣,以进一步提高对刚地弓形虫感染的保护作用,并减少治疗的持续时间和潜在药物耐药的风险。成熟和标准化的动物感染模型是评估有前途的疫苗和化合物候选物的关键因素。尽管近年来在牛和绵羊中的实验研究数量有所增加,但与新孢子虫病相关的绝大多数实验动物实验都是在小鼠中进行的。在这篇综述中,我们讨论了关于刚地弓形虫感染在小鼠和反刍动物中药物和疫苗开发进展的最新发现。

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