基因减毒的P36p缺陷型伯氏疟原虫子孢子可提供持久且部分的跨物种保护。

Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer long-lasting and partial cross-species protection.

作者信息

Douradinha Bruno, van Dijk Melissa R, Ataide Ricardo, van Gemert Geert-Jan, Thompson Joanne, Franetich Jean-François, Mazier Dominique, Luty Adrian J F, Sauerwein Robert, Janse Chris J, Waters Andrew P, Mota Maria M

机构信息

Unidade Malaria, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028, Lisboa, Portugal.

出版信息

Int J Parasitol. 2007 Nov;37(13):1511-9. doi: 10.1016/j.ijpara.2007.05.005. Epub 2007 May 21.

Abstract

Immunisation with live, radiation-attenuated sporozoites (RAS) or genetically attenuated sporozoites (GAS) of rodent plasmodial parasites protects against subsequent challenge infections. We recently showed that immunisation with Plasmodium berghei GAS that lack the microneme protein P36p protects mice for a period of up to 4 months. Here, we show that the period of full protection induced by p36p(-)-sporozoites lasts 12 and 18 months in C57Bl6 and BALB/c mice, respectively. Full protection is also achieved with three doses of only 1000 p36p(-) (but not RAS) sporozoites. Subcutaneous, intradermal or intramuscular routes of administration also lead to partial protection. In addition, immunisation with either P. berghei RAS- or, to a lesser extent, p36p(-)-sporozoites inhibits parasite intrahepatic development in mice challenged with Plasmodium yoelii sporozoites. Since naturally acquired malaria infections or subunit-based vaccines only induce short-term immune responses, the protection conferred by immunisation with p36p(-)-sporozoites described here further emphasises the potential of GAS as a vaccination strategy for malaria.

摘要

用活的、经辐射减毒的疟原虫子孢子(RAS)或基因减毒的疟原虫子孢子(GAS)对啮齿动物疟原虫寄生虫进行免疫接种可预防随后的攻击感染。我们最近表明,用缺乏微小体蛋白P36p的伯氏疟原虫GAS进行免疫接种可使小鼠在长达4个月的时间内得到保护。在此,我们表明,p36p(-)-子孢子诱导的完全保护期在C57Bl6小鼠和BALB/c小鼠中分别持续12个月和18个月。仅用三剂1000个p36p(-)(而非RAS)子孢子也能实现完全保护。皮下、皮内或肌肉注射途径也能产生部分保护作用。此外,用伯氏疟原虫RAS-子孢子或在较小程度上用p36p(-)-子孢子进行免疫接种可抑制受约氏疟原虫子孢子攻击的小鼠体内寄生虫的肝内发育。由于自然获得的疟疾感染或基于亚单位的疫苗仅诱导短期免疫反应,此处所述的用p36p(-)-子孢子进行免疫接种所提供的保护进一步强调了GAS作为疟疾疫苗接种策略的潜力。

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