Abstract Trypanosomes are protozoan parasites that cause infectious diseases including human African trypanosomiasis (sleeping sickness), and nagana in economically-important livestock animals 1,2 . An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms including antigenic variation 3 that present an apparently insurmountable barrier to vaccination. Here we show using a systematic genome-led vaccinology approach 4 and a murine model of Trypanosoma vivax infection 5 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 localised to the flagellum membrane termed “invariant flagellum antigen from T. vivax ” (IFX) induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies to IFX could induce sterile protection and revealed multiple 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 the socioeconomic development of sub-Saharan African countries 6 and challenges long-held views that vaccinating against trypanosome infections cannot be achieved.

An invariant Trypanosoma vivax vaccine antigen inducing protective immunity