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靶向锥虫非变异抗原的疫苗可诱导保护性免疫
2021-05-30 12:41

英国惠康基金桑格研究所Gavin J. Wright课题组近日取得一项新成果。经过不懈努力,他们的研究发现靶向锥虫非变异抗原的疫苗可诱导保护性免疫。2021年5月26日,国学术期刊《自然》发表了这一成果。

使用系统化基于基因组引导的疫苗学方法和活动锥虫感染小鼠模型,研究人员发现了可产生恒定保护性疫苗亚单位的抗原。利用位于鞭毛膜上保守细胞表面蛋白胞外区域的单个重组蛋白进行疫苗接种(研究人员将其称为“来自疟原虫的不变鞭毛抗原”)可诱导长效保护。免疫力通过免疫血清被动转移,针对该蛋白的重组单克隆抗体可以诱导无菌保护,并揭示了抗体介导免疫的几种机制,包括补体的主要作用。

该发现确定了一种针对寄生虫疾病的候选疫苗,该疾病已限制了撒哈拉以南非洲国家的社会经济发展,并提供了该疫苗可针对锥虫感染产生高度保护性的证据。

据介绍,锥虫是能导致传染病的原生动物寄生虫,是造成人类非洲锥虫病(昏睡病)和牲畜疾病的长假虫。靶向锥虫的有效疫苗将是重要的防控工具,但该寄生虫已经进化出复杂的免疫保护机制,包括抗原变异,这显然是疫苗接种中不可逾越的障碍。

附:英文原文

Title: An invariant Trypanosoma vivax vaccine antigen induces protective immunity

Author: Delphine Autheman, Ccile Crosnier, Simon Clare, David A. Goulding, Cordelia Brandt, Katherine Harcourt, Charlotte Tolley, Francis Galaway, Malhar Khushu, Han Ong, Alessandra Romero-Ramirez, Craig W. Duffy, Andrew P. Jackson, Gavin J. Wright

Issue&Volume: 2021-05-26

Abstract: Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock1,2. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms—including antigenic variation3—that present an apparently insurmountable barrier to vaccination. Here we show, using a systematic genome-led vaccinology approach and a mouse model of Trypanosoma vivax infection4, that protective invariant subunit vaccine antigens can be identified. Vaccination with a single recombinant protein comprising the extracellular region of a conserved cell-surface protein that is localized to the flagellum membrane (which we term ‘invariant flagellum antigen from T. vivax’) induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies to this protein could induce sterile protection and revealed several mechanisms of antibody-mediated immunity, including a major role for complement. Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained socioeconomic development in countries in sub-Saharan Africa5, and provides evidence that highly protective vaccines against trypanosome infections can be achieved.

DOI: 10.1038/s41586-021-03597-x

Source: https://www.nature.com/articles/s41586-021-03597-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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