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转基因寄生虫在疟疾疫苗研究中的应用。

The use of transgenic parasites in malaria vaccine research.

作者信息

Othman Ahmad Syibli, Marin-Mogollon Catherin, Salman Ahmed M, Franke-Fayard Blandine M, Janse Chris J, Khan Shahid M

机构信息

a Leiden Malaria Research Group, Parasitology , Leiden University Medical Center (LUMC) , Leiden , the Netherlands.

b Faculty of Health Sciences , Universiti Sultan Zainal Abidin , Terengganu , Malaysia.

出版信息

Expert Rev Vaccines. 2017 Jul;16(7):1-13. doi: 10.1080/14760584.2017.1333426. Epub 2017 May 30.

Abstract

Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.

摘要

表达外源基因(例如荧光蛋白和发光蛋白)的转基因疟原虫被广泛用于探究疟原虫生物学以及与疟疾病理学相关的宿主 - 寄生虫相互作用。转基因寄生虫也越来越多地被用于推进疟疾疫苗的研发。涵盖领域:我们综述了转基因疟原虫如何在体外和体内用于确定不同抗原和疫苗接种策略的保护效力,以及确定保护的免疫相关因素。我们描述了表达恶性疟原虫或间日疟原虫抗原的嵌合啮齿动物疟原虫如何在推进至临床试验之前被用于直接评估人类疟疾疫苗并进行排序。此外,我们描述了转基因人类和啮齿动物疟原虫如何用于开发和评估活(基因)减毒疫苗。专家评论:转基因啮齿动物和人类疟原虫正被用于识别疫苗候选抗原,并在推进至临床试验之前评估亚单位疫苗和全生物体疫苗。转基因寄生虫与体内临床前测试模型(例如小鼠)相结合,用于评估疫苗安全性、效力和保护的持久性,以及揭示关键的保护性免疫反应并完善疫苗接种策略。

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