Authors

D Autheman¹; C Crosnier¹; L Morrison²; A Evans³; H Davies¹; AP Jackson⁴; G Wright¹;  ¹ Department of Biology, Hull York Medical School, UK;  ² Roslin Institute, Royal (Dick) School of Veterinary Studies, UK;  ³ Clinglobal, Mohammedia, Morocco;  ⁴ Department of Infection Biology, University of Liverpool, UK

Discussion

Trypanosomes are protozoan parasites that cause infectious diseases including human African trypanosomiasis (sleeping sickness), and nagana in economically-important livestock animals. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immuno-protective mechanisms including antigenic variation that present an apparently insurmountable barrier to vaccination. Using a systematic genome-led reverse vaccinology approach and murine infection models of Trypanosoma infection, we show 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 induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies could induce sterile protection and revealed multiple mechanisms of antibody-mediated immunity, including a major role for complement. To translate this research we are developing livestock infection models of both Trypanosoma congolense and Trypanosoma vivax that are suitable for testing subunit vaccines. Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained the socioeconomic development of sub-Saharan African countries and challenges long-held views that vaccinating against trypanosome infections cannot be achieved.