State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2022 Oct 25;13:1034820. doi: 10.3389/fimmu.2022.1034820. eCollection 2022.
Nematodes are one of the largest groups of animals on the planet. Many of them are major pathogens of humans, animals and plants, and cause destructive diseases and socioeconomic losses worldwide. Despite their adverse impacts on human health and agriculture, nematodes can be challenging to control, because anthelmintic treatments do not prevent re-infection, and excessive treatment has led to widespread drug resistance in nematode populations. Indeed, many nematode species of livestock animals have become resistant to almost all classes of anthelmintics used. Most efforts to develop commercial anti-nematode vaccines (native or recombinant) for use in animals and humans have not succeeded, although one effective (dead) vaccine (Barbervax) has been developed to protect animals against one of the most pathogenic parasites of livestock animals - (the barber's pole worm). This vaccine contains native molecules, called H11 and H-Gal-GP, derived from the intestine of this blood-feeding worm. In its native form, H11 alone consistently induces high levels (75-95%) of immunoprotection in animals against disease (haemonchosis), but recombinant forms thereof do not. Here, to test the hypothesis that post-translational modification (glycosylation) of H11 plays a crucial role in achieving such high immunoprotection, we explored the N-glycoproteome and N-glycome of H11 using the high-resolution mass spectrometry and assessed the roles of N-glycosylation in protective immunity against . Our results showed conclusively that N-glycan moieties on H11 are the dominant immunogens, which induce high IgG serum antibody levels in immunised animals, and that anti-H11 IgG antibodies can confer specific, passive immunity in naïve animals. This work provides the first detailed account of the relevance and role of protein glycosylation in protective immunity against a parasitic nematode, with important implications for the design of vaccines against metazoan parasites.
线虫是地球上最大的动物群体之一。它们中的许多是人类、动物和植物的主要病原体，在全球范围内造成破坏性疾病和社会经济损失。尽管线虫对线虫对人类健康和农业有不利影响，但很难控制，因为驱虫治疗不能预防再次感染，而且过度治疗导致线虫种群广泛耐药。事实上，许多家畜线虫物种几乎对所有类别的驱虫药都产生了耐药性。尽管已经开发出一种有效的（死）疫苗（ Barbervax ）来保护动物免受最具致病性的家畜寄生虫之一 - （ Barber's pole worm ）的侵害，但大多数开发用于动物和人类的商业抗线虫疫苗（天然或重组）的努力都没有成功。这种疫苗含有天然分子，称为 H11 和 H-Gal-GP，源自这种吸血蠕虫的肠道。在其天然形式下，单独的 H11 一致地在动物中诱导针对疾病（血虫病）的高水平（75-95%）免疫保护，但重组形式则不能。在这里，为了测试 H11 的翻译后修饰（糖基化）在实现这种高免疫保护中的关键作用的假设，我们使用高分辨率质谱法探索了 H11 的 N-糖蛋白组和 N-聚糖组，并评估了 N-糖基化在针对 的保护性免疫中的作用。我们的研究结果明确表明，H11 上的 N-聚糖部分是主要的免疫原，它诱导免疫动物中高 IgG 血清抗体水平，并且抗-H11 IgG 抗体可以在幼稚动物中赋予特异性被动免疫。这项工作首次详细说明了蛋白质糖基化在抗寄生虫线虫保护性免疫中的相关性和作用，对设计针对后生动物寄生虫的疫苗具有重要意义。
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