An invariant Trypanosoma vivax vaccine antigen induces protective immunity

Delphine Autheman, Cécile 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 and Gavin J. Wright ()
Additional contact information
Delphine Autheman: Wellcome Sanger Institute
Cécile Crosnier: Wellcome Sanger Institute
Simon Clare: Wellcome Sanger Institute
David A. Goulding: Wellcome Sanger Institute
Cordelia Brandt: Wellcome Sanger Institute
Katherine Harcourt: Wellcome Sanger Institute
Charlotte Tolley: Wellcome Sanger Institute
Francis Galaway: Wellcome Sanger Institute
Malhar Khushu: Wellcome Sanger Institute
Han Ong: Wellcome Sanger Institute
Alessandra Romero-Ramirez: University of Liverpool
Craig W. Duffy: University of Liverpool
Andrew P. Jackson: University of Liverpool
Gavin J. Wright: Wellcome Sanger Institute

Nature, 2021, vol. 595, issue 7865, 96-100

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03597-x

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