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转基因疟原虫凸显了全寄生虫疫苗策略的潜力。

Genetically modified Plasmodium highlights the potential of whole parasite vaccine strategies.

作者信息

Good Michael F

机构信息

The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane 4029, Australia.

出版信息

Trends Immunol. 2005 Jun;26(6):295-7. doi: 10.1016/j.it.2005.04.005.

DOI:10.1016/j.it.2005.04.005
PMID:15922944
Abstract

A genetically modified malaria sporozoite might breathe new life into the traditional approach to vaccine development, that of using whole organisms. Mueller and colleagues recently knocked out a gene, UIS3, from the rodent parasite, Plasmodium berghei, and demonstrated that the sporozoite forms could not develop beyond the stage of the life cycle in the liver (thus not giving rise to clinical disease, which is associated with blood infection) but could induce protection against subsequent challenge with genetically intact sporozoites. UIS3(-) sporozoites or irradiated sporozoites might find success where subunit approaches are struggling.

摘要

一种经过基因改造的疟原虫子孢子可能会给传统的疫苗开发方法——即使用全生物体的方法——注入新的活力。穆勒及其同事最近从啮齿动物寄生虫伯氏疟原虫中敲除了一个名为UIS3的基因,并证明子孢子形式在肝脏中的生命周期阶段之后无法发育(因此不会引发与血液感染相关的临床疾病),但可以诱导对随后用基因完整的子孢子进行攻击的保护作用。在亚单位方法面临困境的情况下,UIS3(-)子孢子或经辐射的子孢子可能会取得成功。

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引用本文的文献

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Genetically engineered, attenuated whole-cell vaccine approaches for malaria.用于疟疾的基因工程减毒全细胞疫苗方法。
Hum Vaccin. 2010 Jan;6(1):107-13. doi: 10.4161/hv.6.1.9654. Epub 2010 Jan 29.
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Acquired immunity to malaria.获得性疟疾免疫力。
Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents. doi: 10.1128/CMR.00025-08.
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Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity.疟原虫子孢子成熟的蛋白质组分析鉴定出对寄生虫发育和感染性至关重要的新蛋白质。
PLoS Pathog. 2008 Oct;4(10):e1000195. doi: 10.1371/journal.ppat.1000195. Epub 2008 Oct 31.
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Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults.抗体介导的恶性疟原虫生长抑制:与肯尼亚儿童和成人年龄的关系以及对寄生虫血症的保护作用
PLoS One. 2008;3(10):e3557. doi: 10.1371/journal.pone.0003557. Epub 2008 Oct 29.
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Genetically attenuated Plasmodium berghei liver stages persist and elicit sterile protection primarily via CD8 T cells.基因减毒的伯氏疟原虫肝期持续存在,并主要通过CD8 T细胞引发无菌保护。
Am J Pathol. 2007 Jul;171(1):107-15. doi: 10.2353/ajpath.2007.060792.
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Plasmodium yoelii sporozoites with simultaneous deletion of P52 and P36 are completely attenuated and confer sterile immunity against infection.同时缺失P52和P36的约氏疟原虫子孢子完全减毒,并能赋予对感染的无菌免疫力。
Infect Immun. 2007 Aug;75(8):3758-68. doi: 10.1128/IAI.00225-07. Epub 2007 May 21.
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