| Autor: |
Autheman D; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK., Crosnier C; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK., Clare S; Pathogen Support Team, Wellcome Sanger Institute, Hinxton, UK., Goulding DA; Electron and Advanced Light Microscopy, Wellcome Sanger Institute, Hinxton, UK., Brandt C; Pathogen Support Team, Wellcome Sanger Institute, Hinxton, UK., Harcourt K; Pathogen Support Team, Wellcome Sanger Institute, Hinxton, UK., Tolley C; Pathogen Support Team, Wellcome Sanger Institute, Hinxton, UK., Galaway F; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK., Khushu M; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK., Ong H; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK., Romero-Ramirez A; Department of Infection Biology and Microbiomes, University of Liverpool, Liverpool, UK., Duffy CW; Department of Infection Biology and Microbiomes, University of Liverpool, Liverpool, UK., Jackson AP; Department of Infection Biology and Microbiomes, University of Liverpool, Liverpool, UK., Wright GJ; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Hinxton, UK. gw2@sanger.ac.uk.; Department of Biology, University of York, York, UK. gw2@sanger.ac.uk.; Hull York Medical School, University of York, York, UK. gw2@sanger.ac.uk.; York Biomedical Research Institute, University of York, York, UK. gw2@sanger.ac.uk. |
| Abstrakt: |
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 variation 3 -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 infection 4 , 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 Africa 5 , and provides evidence that highly protective vaccines against trypanosome infections can be achieved. |
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