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Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

机译:针对人类疟疾寄生虫恶性疟原虫裂殖子表面蛋白1的抗体分析

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The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.
机译:疟原虫生命周期中不可或缺的恶性疟原虫的190 kDa裂殖子表面蛋白1(MSP-1)是疟疾疫苗的主要候选对象。分析了异源产生的MSP-1加工产物p83,p30,p38和p42(衍生自3D7株)引起的兔抗体潜在的体外抑制寄生虫和寄生虫生长侵袭红细胞的潜力。我们的数据表明(i)抑制寄生虫复制的抗体识别的表位分布在整个MSP-1分子中; (ii)合并后,对MSP-1不同区域具有特异性的抗体会以严格加和的方式抑制; (iii)抗MSP-1抗体会干扰红细胞的入侵以及寄生虫的红细胞内生长; (iv)针对菌株3D7的MSP-1产生的抗体强烈交叉抑制异源菌株FCB-1的复制。因此,抗MSP-1抗体似乎能够在多于一个水平上干扰寄生虫繁殖。由于MSP-1在兔子中的总体免疫原性与在用寄生虫来源的MSP-1免疫的 Aotus 猴子的血清中和对疟疾半免疫的人的血清中非常相似,疟疾对其高度抑制抗原特异性已回收抗体,我们认为此处报道的发现与开发基于MSP-1的抗疟疾疫苗有关。

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