Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3.

Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3.
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DOI:
10.1111/j.1365-3024.2007.00951.x
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发表时间:
2007-08
影响因子:
2.2
通讯作者:
Marsh K
Marsh K
中科院分区:
医学4区
文献类型:
--
作者:
Osier FH;Polley SD;Mwangi T;Lowe B;Conway DJ;Marsh K

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许多关于裂殖子表面蛋白3(MSP 3)在抗疟疾免疫中作用的研究都集中在MSP 3的保守部分。新的证据表明,MSP 3内的多态性序列受到免疫选择。我们报告了一个详细的分析自然获得的抗体等位基因特异性和保守的部分MSP 3在肯尼亚的队列。对异源重组MSP 3蛋白的间接和竞争ELISA用于抗体测定,并对寄生虫进行msp 3等位基因的基因分型。抗体对MSP 3等位基因特异性和保守表位的反应性在个体之间是异质的。总体而言,等位基因特异性抗体反应性的发生率(3D 7特异性54%,K1特异性41%)显著高于代表C-末端MSP 3保守部分的重组蛋白(24%,P <0.01)。最丰富的IgG亚类是IgG 3,其次是IgG 1。在疟疾传播季节开始时被寄生的个体中,对MSP 3的K1型的等位基因特异性反应与6个月随访期间临床疟疾发作的风险较低相关(相对风险0.41,95%置信区间0.20 - 0.81,P = 0.011)。在MSP 3疟疾疫苗的开发中,除了对保守表位的免疫外,还应考虑对MSP 3的等位基因特异性免疫的潜在重要性。
Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogenous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P < 0·01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes during a 6-month follow-up in individuals who were parasitized at the start of the malaria transmission season (Relative risk 0·41 with 95% confidence interval 0·20–0·81, P = 0·011). The potential importance of allele-specific immunity to MSP3 should be considered in addition to immunity to conserved epitopes, in the development of an MSP3 malaria vaccine.
DOI: 10.1086/430006
发表时间: 2005-06-01
影响因子: 6.4
作者:
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发表时间: 2005-11
期刊: PLoS medicine
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发表时间: 2002-03-01
影响因子: 3.6
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DOI: 10.1086/509806
发表时间: 2007-01-15
影响因子: 6.4
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通讯作者: Conway, David J.