疟疾每年导致上百万死亡。来自澳大利亚墨尔本市贝尼特研究所(Burnet Institute)的研究人员在寻找抵抗疟疾的疫苗过程中取得一项重大突破：他们揭开被称作变异性表面蛋白(variant surface antigens, VSAs)的疟原虫蛋白的秘密。他们将研究结果发表在Journal of Clinical Investigation期刊上。
在这项研究中，研究人员揭示出一种靶标在免疫系统抵抗疟疾中发挥着关键性作用。这些发现表明对疟疾产生免疫性的人们产生主要靶向蛋白PfEMP1的抗体，其中PfEMP1是由导致大多数疟疾产生的致病微生物恶性疟原虫(Plasmodium falciparum)产生的。
论文通讯作者、贝尼特研究所免疫学中心主任James Beeson教授说，这些新发现有助于开发刺激免疫系统的疫苗以便能够特异性地对疟原虫产生的蛋白PfEMP1产生强烈的免疫反应。
论文共同第一作者Jo-Anne Chan说，这项研究也表明尽管免疫系统也攻击疟原虫产生的其他蛋白，但是这并不能有效地保护人们免疫感染。这就说明免疫系统必须正确地攻击合适的蛋白才能有效地抵抗疟原虫感染。她说，对肯尼亚儿童的研究表明携带针对蛋白PfEMP1的抗体的儿童显著性降低患上疟疾的风险，而携带针对其他表面抗原的抗体的儿童不能获得相应的保护性免疫。(生物谷：Bioon.com)
本文编译自Lifting malaria's deadly veil: mystery solved in quest for vaccine
doi: 10.1172/JCI62182
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Targets of antibodies against Plasmodium falciparum–infected erythrocytes in malaria immunity
Jo-Anne Chan1,2,3, Katherine B. Howell2, Linda Reiling1,2, Ricardo Ataide4, Claire L. Mackintosh5, Freya J.I. Fowkes1,2,6, Michaela Petter4, Joanne M. Chesson2, Christine Langer1, George M. Warimwe5, Michael F. Duffy4, Stephen J. Rogerson4, Peter C. Bull5, Alan F. Cowman2,3, Kevin Marsh5 and James G. Beeson
Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum–infected erythrocytes (P. falciparum–IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.
