A highly infectious Plasmodium yoelii parasite, bearing Plasmodium falciparum circumsporozoite protein.
A highly infectious Plasmodium yoelii parasite, bearing Plasmodium falciparum circumsporozoite protein.
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DOI：
10.1186/s12936-016-1248-z
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发表时间：
2016-04-12
期刊：
影响因子：
3
通讯作者：
Tsuji M
中科院分区：
文献类型：
--
作者：
Zhang M;Kaneko I;Tsao T;Mitchell R;Nardin EH;Iwanaga S;Yuda M;Tsuji M
疟原虫环子孢子蛋白（CSP）是疟原虫子孢子（Spz）阶段的主要表面抗原。RTS，S疫苗是临床上最先进的疟疾疫苗，由大部分恶性疟原虫CSP（PfCSP）组成。需要一种高感染性的重组啮齿类疟疾，携带全长PfCSP的约氏疟原虫，PfCSP/Py Spz，作为一种工具来评估PfCSP在小鼠模型中介导保护性抗疟疾免疫中的作用。通过双交换同源重组将表达PfCSP的构建体插入约氏疟原虫CSP基因的基因座，产生转基因寄生虫PfCSP/Py Spz。并对PfCSP/Py Spz的生物学和防护性能进行了测定。这种PfCSP/Py寄生虫在蚊子唾液腺中产生高达30，000个Spz，这等于或甚至高于野生型约氏疟原虫产生的Spz数量。PfCSP/Py感染的蚊虫叮咬5次可引起BALB/c小鼠血液感染。目前的研究已经证明成功建立了能够表达全长PfCSP（PfCSP/Py寄生虫）的转基因约氏疟原虫寄生虫克隆。重要的是，这种PfCSP/Py寄生虫在蚊子载体和小鼠（哺乳动物宿主）中可以与野生型约氏疟原虫一样具有感染性。一种新的表达全长PfCSP的转基因寄生虫可能成为研究人员在小鼠模型中研究针对PfCSP的免疫力的有用工具。
Plasmodium circumsporozoite protein (CSP) is a major surface antigen present in the sporozoite (Spz) stage of a malaria parasite. RTS, S vaccine, the most clinically advanced malaria vaccine, consists of a large portion of Plasmodium falciparum CSP (PfCSP). A highly infectious, recombinant rodent malaria, Plasmodium yoelii parasite bearing a full-length PfCSP, PfCSP/Py Spz, was needed as a tool to evaluate the role of PfCSP in mediating, protective, anti-malaria immunity in a mouse model. A transgenic parasite, PfCSP/Py Spz, was generated by inserting a construct expressing the PfCSP at the locus of the P. yoelii CSP gene by double cross-over homologous recombination. Then the biological and protective properties of PfCSP/Py Spz were determined. This PfCSP/Py parasite produced up to 30,000 Spz in mosquito salivary glands, which is equal or even higher than the number of Spz produced by wild-type P. yoelii parasites. Five bites of PfCSP/Py-infected mosquitoes could induce blood infection in BALB/c mice. The current study has demonstrated a successful establishment of a transgenic P. yoelii parasite clone that is able to express a full-length PfCSP, PfCSP/Py parasite. Importantly, this PfCSP/Py parasite can be as infectious as the wild-type P. yoelii parasite both in mosquito vector and in mouse, a mammalian host. A new transgenic parasite that expresses a full-length PfCSP may become a useful tool for researchers to investigate immunity against PfCSP in a mouse model.