疟原虫 falciparum MSP1 阻断 4 型 IgM 和 IgG 反应表位优势的转变

Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4.

机构信息

John A Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St, Honolulu, HI 96813, USA.

出版信息

Malar J. 2010 Jan 13;9:14. doi: 10.1186/1475-2875-9-14.

DOI:10.1186/1475-2875-9-14

PMID:20070906

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2837054/

Abstract

BACKGROUND

Plasmodium falciparum merozoite surface protein-1 (MSP1) has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17) and the hypervariable N-terminal repeat region (block 2). However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene.

METHODS

The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7) in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition.

RESULTS

IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%), with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations.

CONCLUSIONS

Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important in isolate-specific immunity to P. falciparum.

摘要

背景

恶性疟原虫裂殖子表面蛋白-1（MSP1）作为一种血期疟疾疫苗候选物已得到广泛研究，大多数工作集中在保守的 19 kDa 和半保守的 42 kDa C 端区域（块 16-17）和高度可变的 N 端重复区域（块 2）。然而，最近的基因分型研究表明，MSP1 的其他区域可能受到选择压力的影响，包括基因 3' 区域内的一个基因内重组位点，称为块 4。

方法

本研究检测了来自哥伦比亚、巴布亚新几内亚和喀麦隆的研究人群对两种亲本和两种重组形式的块 4 以及块 16-17（3D7）的抗体反应，这些人群在疟疾传播强度和种族构成上存在差异。

结果

在所有三个人群中，均检测到针对亲本和重组 MSP1 块 4 肽的 IgM 和 IgG 抗体。总体而言，32-44%的个体产生了一种或多种肽的 IgM，大多数个体的 IgM 抗体对亲本和重组形式均有反应。相比之下，块 4 的 IgG 血清阳性率在人群中有所不同（范围为 15-65%），大多数抗体显示对一个或一对块 4 肽具有特异性。块 4 的 IgG 反应明显低于块 16-17，表明块 4 是次要的。块 4 和块 16-17 的抗体显示出不同的 IgG 亚类偏向，块 4 反应偏向 IgG3，块 16-17 反应偏向 IgG1。这些反应模式在三个研究人群中均一致观察到。