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vivaxin 基因在间日疟原虫细胞表面编码高度免疫原性、非变异的抗原。

Vivaxin genes encode highly immunogenic, non-variant antigens on the Trypanosoma vivax cell-surface.

机构信息

Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

出版信息

PLoS Negl Trop Dis. 2022 Sep 21;16(9):e0010791. doi: 10.1371/journal.pntd.0010791. eCollection 2022 Sep.

Abstract

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.

摘要

布氏锥虫是一种单细胞血原虫,也是动物非洲锥虫病(AAT)的主要病原体,这种疾病通过媒介传播,对撒哈拉以南非洲的牲畜具有潜在致命性。此前,我们已经鉴定出多种布氏锥虫特有的基因,这些基因预测编码细胞表面蛋白。在此,我们研究了自然感染和实验感染宿主对这些独特寄生虫抗原的免疫反应,以确定可能成为疫苗候选物的免疫原。宿主血清的免疫分析表明,一个特定的家族(Fam34)会引起一致的 IgG 抗体反应。这个基因家族,我们现在称之为 Vivaxin,编码至少 124 个跨膜糖蛋白,它们表现出截然不同的表达谱和遗传变异模式。我们专注于一个基因(viv-β8),该基因编码一种特别免疫原性的 vivaxin 蛋白,在感染过程中高度表达,但在整个寄生虫群体中表现出最小的多态性。用 Quil-A 佐剂对小鼠进行 VIVβ8 疫苗接种会引发强烈、平衡的免疫反应,并在一些动物中延迟寄生虫增殖,但最终无法预防疾病。尽管 VIVβ8 定位于细胞体和鞭毛膜,但活体免疫染色表明,VIVβ8 在体内基本上无法被抗体识别。然而,我们的系统发育分析表明,vivaxin 包含其他最近被证明能诱导针对布氏锥虫免疫的抗原。因此,引入 vivaxin 代表了我们对布氏锥虫细胞表面理解的重要进展。除了作为已证实和有前途的疫苗抗原的来源外,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-寄生虫相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6531/9529106/963494c0dc1d/pntd.0010791.g001.jpg

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