Nature. 2021 May 26. doi: 10.1038/s41586-021-03597-x. Epub ahead of print. PMID: 34040257.
Autheman D, Crosnier C, Clare S, Goulding DA, Brandt C, Harcourt K, Tolley C, Galaway F, Khushu M, Ong H, Romero-Ramirez A, Duffy CW, Jackson AP, Wright GJ.
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.
- Morrison, L. J., Vezza, L., Rowan, T. & Hope, J. C. Animal African trypanosomiasis: time to increase focus on clinically relevant parasite and host species. Trends Parasitol. 32, 599–607 (2016).
- Büscher, P., Cecchi, G., Jamonneau, V. & Priotto, G. Human African trypanosomiasis. Lancet 390, 2397–2409 (2017).
- Horn, D. Antigenic variation in African trypanosomes. Mol. Biochem. Parasitol. 195, 123–129 (2014).
- D’Archivio, S. et al. Non-invasive in vivo study of the Trypanosoma vivax infectious process consolidates the brain commitment in late infections. PLoS Negl. Trop. Dis. 7, e1976 (2013).
- Budd, L. T. DFID-funded Tsetse and Trypanosome Research and Development Since 1980. Vol. 2. Economic Analysis (DFID Livestock Production, Animal Health and Natural Resources Systems Research Programmes, 1999).