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人类志愿者中针对恶性疟原虫红细胞膜蛋白1的抗体反应特征

Characterization of the antibody response against Plasmodium falciparum erythrocyte membrane protein 1 in human volunteers.

作者信息

Krause Darren R, Gatton Michelle L, Frankland Sarah, Eisen Damon P, Good Michael F, Tilley Leann, Cheng Qin

机构信息

Malaria Drug Resistance and Chemotherapy, Infectious Diseases and Immunology Division, The Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Qld 4029, Australia.

出版信息

Infect Immun. 2007 Dec;75(12):5967-73. doi: 10.1128/IAI.00327-07. Epub 2007 Oct 8.

Abstract

The immune response against the Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria. In this study, we used sera from human volunteers who had been infected with the P. falciparum 3D7 strain to investigate the development, specificity, and dynamics of anti-PfEMP1 antibodies measured against six different strain 3D7 Duffy binding-like domain 1alpha (DBL1alpha) fusion proteins. We observed that a parasitemia of 20 to 200 infected erythrocytes per mul was required to trigger an antibody response to DBL1alpha and that antibodies against one DBL1alpha variant cross-react with other DBL1alpha variants. Both serum and purified immunoglobulin Gs (IgGs) were able to agglutinate infected erythrocytes, and purified anti-DBL1alpha IgGs bound to the live infected red blood cell surface in a punctate surface pattern, confirming that the IgGs recognize native PfEMP1. Analysis of sera from tourists naturally infected with P. falciparum suggests that the anti-PfEMP1 antibodies often persisted for more than 100 days after a single infection. These results help to further our understanding of the development of acquired immunity to P. falciparum infections.

摘要

针对恶性疟原虫变异表面抗原恶性疟原虫红细胞膜蛋白1(PfEMP1)的免疫反应是临床抗恶性疟免疫的关键组成部分。在本研究中,我们使用感染了恶性疟原虫3D7株的人类志愿者的血清,来研究针对六种不同菌株3D7达菲结合样结构域1α(DBL1α)融合蛋白所检测到的抗PfEMP1抗体的产生、特异性和动态变化。我们观察到,每微升血液中20至200个感染红细胞的寄生虫血症水平是触发针对DBL1α的抗体反应所必需的,并且针对一种DBL1α变体的抗体与其他DBL1α变体发生交叉反应。血清和纯化的免疫球蛋白G(IgG)均能够凝集感染的红细胞,并且纯化的抗DBL1α IgG以点状表面模式结合到活的感染红细胞表面,证实这些IgG识别天然的PfEMP1。对自然感染恶性疟原虫的游客血清的分析表明,抗PfEMP1抗体在单次感染后通常会持续超过100天。这些结果有助于进一步加深我们对获得性抗恶性疟原虫感染免疫力发展的理解。

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