Vivaxin genes encode highly immunogenic, non-variant antigens on the Trypanosoma vivax cell-surface.
Vivaxin genes encode highly immunogenic, non-variant antigens on the Trypanosoma vivax cell-surface.
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DOI：
10.1371/journal.pntd.0010791
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发表时间：
2022-09
影响因子：
3.8
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中科院分区：
文献类型：
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间日锥虫是一种单细胞血液寄生虫，是动物非洲锥虫病 (AAT) 的主要原因，非洲锥虫病是撒哈拉以南非洲地区一种媒介传播的、可能致命的牲畜疾病。此前，我们鉴定了多种间日疟原虫特异性基因，预计这些基因可编码细胞表面蛋白。在这里，我们检查自然和实验感染宿主对这些独特寄生虫抗原的免疫反应，以确定可以成为候选疫苗的免疫原。宿主血清的免疫分析显示，一个特定家族 (Fam34) 能引发一致的 IgG 抗体反应。这个基因家族，我们现在称为 Vivaxin，编码至少 124 个跨膜糖蛋白，这些蛋白显示出相当不同的表达谱和遗传变异模式。我们重点关注一种基因 (viv-β8)，该基因编码一种特别具有免疫原性的 vivaxin 蛋白，该蛋白在感染过程中高度表达，但在寄生虫群体中表现出最小的多态性。给小鼠接种以 Quil-A 为佐剂的 VIVβ8 疫苗会引发强烈、平衡的免疫反应，并延迟某些动物体内的寄生虫增殖，但最终并不能预防疾病。尽管 VIVβ8 位于细胞体和鞭毛膜上，但活体免疫染色表明体内抗体基本上无法接近 VIVβ8。然而，我们的系统发育分析表明，间日疟原虫蛋白包括最近显示可诱导针对间日疟原虫免疫的其他抗原。因此，间日疟原虫的引入代表了我们对间日疟原虫细胞表面的理解的重要进展。除了是经过验证和有前途的疫苗抗原的来源之外，该基因家族显然是寄生虫糖萼的重要组成部分，有可能影响宿主与寄生虫的相互作用。非洲动物锥虫病 (AAT) 是撒哈拉以南非洲及其他地区的一种重要牲畜疾病。 AAT 是由间日锥虫等物种引起的，这是一种单细胞寄生虫，通过叮咬采采蝇传播并在血液和其他组织中繁殖，如果不及时治疗，通常会导致致命的神经系统疾病。尽管协调一致的药物治疗和病媒根除计划已成功控制了非洲人类锥虫病，但 AAT 继续对动物健康产生不利影响，并阻碍许多欠发达国家的高效粮食生产和经济发展。在这项研究中，我们试图鉴定在自然感染的动物中刺激最强免疫反应的寄生虫表面蛋白，作为疫苗的基础。我们描述了在间日疟原虫中发现的一种新的物种特异性蛋白质家族，我们将其称为间日疟原虫蛋白。我们发现，一种 vivaxin 蛋白 (VIVβ8) 是表面表达的，当用于免疫小鼠时可以延缓寄生虫增殖，但不能预防感染。尽管如此，我们还发现 vivaxin 包含另一种先前显示可诱导保护性免疫的蛋白质 (IFX/VIVβ1)。除了其在 AAT 控制新方法方面的巨大潜力外，vivaxin 家族还被发现是间日疟原虫细胞表面的重要组成部分，并且可能在宿主相互作用中具有重要的物种特异性作用。
Trypanosoma vivax is a unicellular hemoparasite, and a principal cause of animal African trypanosomiasis (AAT), a vector-borne and potentially fatal livestock disease across sub-Saharan Africa. Previously, we identified diverse T. vivax-specific genes that were predicted to encode cell surface proteins. Here, we examine the immune responses of naturally and experimentally infected hosts to these unique parasite antigens, to identify immunogens that could become vaccine candidates. Immunoprofiling of host serum shows that one particular family (Fam34) elicits a consistent IgG antibody response. This gene family, which we now call Vivaxin, encodes at least 124 transmembrane glycoproteins that display quite distinct expression profiles and patterns of genetic variation. We focused on one gene (viv-β8) that encodes one particularly immunogenic vivaxin protein and which is highly expressed during infections but displays minimal polymorphism across the parasite population. Vaccination of mice with VIVβ8 adjuvanted with Quil-A elicits a strong, balanced immune response and delays parasite proliferation in some animals but, ultimately, it does not prevent disease. Although VIVβ8 is localized across the cell body and flagellar membrane, live immunostaining indicates that VIVβ8 is largely inaccessible to antibody in vivo. However, our phylogenetic analysis shows that vivaxin includes other antigens shown recently to induce immunity against T. vivax. Thus, the introduction of vivaxin represents an important advance in our understanding of the T. vivax cell surface. Besides being a source of proven and promising vaccine antigens, the gene family is clearly an important component of the parasite glycocalyx, with potential to influence host-parasite interactions. Animal African trypanosomiasis (AAT) is an important livestock disease throughout sub-Saharan Africa and beyond. AAT is caused by Trypanosoma vivax, among other species, a unicellular parasite that is spread by biting tsetse flies and multiplies in the bloodstream and other tissues, leading to often fatal neurological conditions if untreated. Although concerted drug treatment and vector eradication programmes have succeeded in controlling Human African trypanosomiasis, AAT continues to adversely affect animal health and impede efficient food production and economic development in many less-developed countries. In this study, we attempted to identify parasite surface proteins that stimulated the strongest immune responses in naturally infected animals, as the basis for a vaccine. We describe the discovery of a new, species-specific protein family in T. vivax, which we call vivaxin. We show that one vivaxin protein (VIVβ8) is surface expressed and retards parasite proliferation when used to immunize mice, but does not prevent infection. Nevertheless, we also reveal that vivaxin includes another protein previously shown to induce protective immunity (IFX/VIVβ1). Besides its great potential for novel approaches to AAT control, the vivaxin family is revealed as a significant component of the T. vivax cell surface and may have important, species-specific roles in host interactions.
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影响因子：
3.3
作者：
Durante IM;Butenko A;Rašková V;Charyyeva A;Svobodová M;Yurchenko V;Hashimi H;Lukeš J
通讯作者：
Lukeš J
影响因子：
4
作者：
Elton, Catherine M.;Rodriguez, Marilis;Wright, Gavin J.
通讯作者：
Wright, Gavin J.
影响因子：
5.5
作者：
Ghosh, A;Zhang, WW;Matlashewski, G
通讯作者：
Matlashewski, G
影响因子：
64.5
作者：
Engstler, Markus;Pfohl, Thomas;Overath, Peter
通讯作者：
Overath, Peter
影响因子：
3.2
作者：
Bakari, Soale Majeed;Ofori, Jennifer Afua;Gwira, Theresa Manful
通讯作者：
Gwira, Theresa Manful