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Merozoite Surface Protein 4/5 Provides Protection against Lethal Challenge with a Heterologous Malaria Parasite Strain

机译:裂殖子表面蛋白4/5通过异源疟疾寄生虫菌株提供抗致命攻击的保护

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Immunization with merozoite surface protein 4/5 (MSP4/5), the murine malaria homologue of Plasmodium falciparum MSP4 and MSP5, has been shown to protect mice against challenge by parasites expressing the homologous form of the protein. The gene encoding MSP4/5 was sequenced from a number of Plasmodium yoelii isolates in order to assess the level of polymorphism in the protein. The gene was found to be highly conserved among the 13 P. yoelii isolates sequenced, even though many of the same isolates showed pronounced variability in their MSP119 sequences. Nonsynonymous mutations were detected only for the isolates Plasmodium yoelii nigeriensis N67 and Plasmodium yoelii killicki 193L and 194ZZ. Immunization and challenge of BALB/c mice showed that the heterologous MSP4/5 proteins were able to confer a level of protection against lethal Plasmodium yoelii yoelii YM challenge infection similar to that induced by immunization with the homologous MSP4/5 protein. To explore the limits of heterologous protection, mice were immunized with recombinant MSP4/5 protein from Plasmodium berghei ANKA and Plasmodium chabaudi adami DS and challenged with P. y. yoelii YM. Interestingly, significant protection was afforded by P. berghei ANKA MSP4/5, which shows 81% sequence identity with P. y. yoelii YM MSP4/5, but it was abolished upon reduction and alkylation. Significant protection was not observed for mice immunized with recombinant P. c. adami DS MSP4/5, which shows 55.7% sequence identity with P. y. yoelii YM MSP4/5. This study demonstrates the robustness of MSP4/5 in conferring protection against variant forms of the protein in a murine challenge system, in contrast to the situation found for other asexual-stage proteins, such as MSP119 and AMA1.
机译:裂殖子表面疟原虫MSP4和MSP5的鼠疟原虫裂殖子表面蛋白4/5(MSP4 / 5)免疫显示,可以保护小鼠免受表达该蛋白同源形式的寄生虫的攻击。为了评估蛋白质中多态性的水平,从许多约氏疟原虫分离物中对编码MSP4 / 5的基因进行了测序。发现该基因在13个 P中高度保守。 yoelii 分离株已测序,尽管许多相同的分离株在其MSP1 19 序列中表现出明显的变异性。仅检测到分离株约氏疟原虫 N67和约氏疟原虫killicki 193L和194ZZ的非同义突变。对BALB / c小鼠的免疫和攻击表明,异源MSP4 / 5蛋白能够赋予一定水平的致死性 Pyomodium yoelii yoelii yoelii YM挑战性感染保护,类似于用同源MSP4 / 5种蛋白质。为了探究异源保护的局限性,用来自伯氏疟原虫 ANKA和 chabaudi chabaudi adami DS的重组MSP4 / 5蛋白免疫小鼠,并用 P攻击。 y。 yoelii YM。有趣的是, P提供了重要的保护。 berghei ANKA MSP4 / 5,与 P具有81%的序列同一性。 y。 yoelii YM MSP4 / 5,但在还原和烷基化后被废除。用重组 P免疫的小鼠未观察到明显的保护作用。 C。 adami DS MSP4 / 5,与 P的序列同一性为55.7%。 y。 yoelii YM MSP4 / 5。这项研究证明了MSP4 / 5在鼠类攻击系统中对蛋白质变体形式提供保护的鲁棒性,与其他无性阶段蛋白质(如MSP1 19 和AMA1)发现的情况相反。

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