Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock^1,2. 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.

锥虫是导致传染病的原生动物寄生虫，包括人类的非洲锥虫病（昏睡病）和具有重要经济意义的牲畜的那加那虫病^1,2。一种有效的锥虫疫苗将是一种重要的控制工具，但这种寄生虫已经进化出复杂的免疫保护机制——包括抗原变异^3——这对疫苗接种来说显然是无法逾越的障碍。我们在这里展示，使用系统的基因组主导的疫苗学方法和间日锥虫感染的小鼠模型⁴, 可以识别保护性不变亚单位疫苗抗原。用包含位于鞭毛膜上的保守细胞表面蛋白的细胞外区域的单一重组蛋白进行疫苗接种（我们将其称为“来自T. vivax的不变鞭毛抗原”）诱导了持久的保护。免疫力是通过免疫血清被动转移的，针对这种蛋白质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。我们的发现确定了一种重要寄生虫病的候选疫苗，这种疾病限制了撒哈拉以南非洲国家的社会经济发展⁵，并提供证据表明可以实现针对锥虫感染的高度保护性疫苗。