A RECOMBINANT 15-KILODALTON CARBOXYL-TERMINAL FRAGMENT OF PLASMODIUM-YOELII-YOELII 17XL MEROZOITE SURFACE PROTEIN-1 INDUCES A PROTECTIVE IMMUNE-RESPONSE IN MICE
A RECOMBINANT 15-KILODALTON CARBOXYL-TERMINAL FRAGMENT OF PLASMODIUM-YOELII-YOELII 17XL MEROZOITE SURFACE PROTEIN-1 INDUCES A PROTECTIVE IMMUNE-RESPONSE IN MICE
复制标题
DOI：
10.1128/iai.61.6.2462-2467.1993
复制
发表时间：
1993-06-01
影响因子：
3.1
通讯作者：
LONG, CA
中科院分区：
文献类型：
--
作者：
DALY, TM;LONG, CA
由于在红细胞内复制的疟疾寄生虫的发育阶段与该病相关的发病率和死亡率有关，因此这些阶段产生的抗原已被提议作为疫苗的候选。在实验系统中，裂殖子的一种表面蛋白(MSP-1)已被证明能免疫啮齿动物和灵长类动物抵御强毒攻击感染。然而，对分子上的相关表位知之甚少，而且试图获得天然构型的重组MSP-1多肽被证明是困难的。我们发现，啮齿动物疟原虫约氏疟原虫MSP-1蛋白的富含半胱氨酸的羧基末端区域可以在大肠杆菌中以天然构型作为融合蛋白表达。该重组多肽含有15 kDa的预测197 kDa蛋白，可在小鼠体内诱导识别本地寄生虫MSP-1的抗体。最重要的是，用Ribi佐剂中的融合蛋白免疫的近交系和近交系小鼠部分地、在某些情况下完全免受致死寄生虫株的攻击感染。这是第一次观察到在重组系统中产生的一小部分MSP-1获得了如此显著的保护。
Since the developmental stages of malarial parasites which replicate within erythrocytes are responsible for the morbidity and mortality associated with this disease, antigens produced by these stages have been proposed as candidates for a vaccine. One surface protein of merozoites (MSP-1) has been shown to immunize both rodents and primates against virulent challenge infection in experimental systems. However, little is known of relevant epitopes on the molecule, and attempts to obtain recombinant MSP-1 polypeptides in a native configuration have proven difficult. We have found that the cysteine-rich, carboxyl-terminal region of the MSP-1 protein from the rodent malarial parasite Plasmodium yoelii yoelii can be expressed in a native configuration as a fusion protein in Escherichia coli. This recombinant polypeptide containing 15 kDa of the predicted 197-kDa protein elicits antibodies in mice which recognize the native parasite MSP-1. Most significantly, both inbred and outbred mice immunized with the fusion protein in Ribi adjuvant are partially and in some cases completely protected against challenge infection with an otherwise lethal parasite strain. This is the first observation of such significant protection obtained with a small portion of the MSP-1 produced in recombinant systems.