Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.

Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.
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DOI:
10.1084/jem.193.12.1403
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发表时间:
2001-06-18
影响因子:
15.3
通讯作者:
Crabb, B S
Crabb, B S
中科院分区:
医学1区
文献类型:
--
作者:
O'Donnell, R A;de Koning-Ward, T F;Burt, R A;Bockarie, M;Reeder, J C;Cowman, A F;Crabb, B S

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与疟原虫裂殖子形式上表达的抗原结合的抗体可以通过阻止裂殖子侵入红细胞来抑制疟原虫生长。在疟疾免疫个体的血清中发现了抑制性抗体,然而,对这一过程重要的那些抗体的特异性尚不清楚。在本文中,我们已经使用等位基因置换构建了一个恶性疟原虫寄生虫系,表达完整的COOH末端片段裂殖子表面蛋白(MSP)-119从不同的啮齿动物疟疾P.夏氏疟原虫。通过将该转染系与仅在MSP-119中不同的亲本寄生虫进行比较,我们表明,对该结构域具有特异性的抗体是恶性疟原虫免疫人类和夏氏疟原虫免疫小鼠中抑制反应的主要组分。在一些个体人血清中,MSP-119抗体主导抑制活性。针对单一蛋白质的小区域的抗体在该过程中起主要作用的发现对疟疾免疫具有重要意义,并且强烈支持进一步理解和开发基于MSP-119的疫苗。
Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-119 antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-119–based vaccines.