瘧疾每年導(dǎo)致上百萬死亡,。來自澳大利亞墨爾本市貝尼特研究所(Burnet Institute)的研究人員在尋找抵抗瘧疾的疫苗過程中取得一項重大突破：他們揭開被稱作變異性表面蛋白(variant surface antigens, VSAs)的瘧原蟲蛋白的秘密。他們將研究結(jié)果發(fā)表在Journal of Clinical Investigation期刊上,。
在這項研究中,，研究人員揭示出一種靶標(biāo)在免疫系統(tǒng)抵抗瘧疾中發(fā)揮著關(guān)鍵性作用。這些發(fā)現(xiàn)表明對瘧疾產(chǎn)生免疫性的人們產(chǎn)生主要靶向蛋白PfEMP1的抗體,，其中PfEMP1是由導(dǎo)致大多數(shù)瘧疾產(chǎn)生的致病微生物惡性瘧原蟲(Plasmodium falciparum)產(chǎn)生的,。
論文通訊作者、貝尼特研究所免疫學(xué)中心主任James Beeson教授說,，這些新發(fā)現(xiàn)有助于開發(fā)刺激免疫系統(tǒng)的疫苗以便能夠特異性地對瘧原蟲產(chǎn)生的蛋白PfEMP1產(chǎn)生強(qiáng)烈的免疫反應(yīng),。
論文共同第一作者Jo-Anne Chan說，這項研究也表明盡管免疫系統(tǒng)也攻擊瘧原蟲產(chǎn)生的其他蛋白,，但是這并不能有效地保護(hù)人們免疫感染,。這就說明免疫系統(tǒng)必須正確地攻擊合適的蛋白才能有效地抵抗瘧原蟲感染。她說,，對肯尼亞兒童的研究表明攜帶針對蛋白PfEMP1的抗體的兒童顯著性降低患上瘧疾的風(fēng)險,，而攜帶針對其他表面抗原的抗體的兒童不能獲得相應(yīng)的保護(hù)性免疫。(生物谷：Bioon.com)
本文編譯自Lifting malaria's deadly veil: mystery solved in quest for vaccine
doi: 10.1172/JCI62182
PMC:
PMID:
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.
