An invariant <i>Trypanosoma vivax</i> vaccine antigen induces protective immunity



Autheman, Delphine, Crosnier, Cecile, Clare, Simon, Goulding, David A, Brandt, Cordelia, Harcourt, Katherine, Tolley, Charlotte, Galaway, Francis, Khushu, Malhar, Ong, Han
et al (show 4 more authors) (2021) An invariant <i>Trypanosoma vivax</i> vaccine antigen induces protective immunity. NATURE, 595 (7865). 96-+.

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Abstract

Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock<sup>1,2</sup>. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms-including antigenic variation<sup>3</sup>-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<sup>4</sup>, 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<sup>5</sup>, and provides evidence that highly protective vaccines against trypanosome infections can be achieved.

Item Type: Article
Uncontrolled Keywords: Flagella, Animals, Mice, Inbred BALB C, Mice, Trypanosoma vivax, Trypanosomiasis, African, Disease Models, Animal, Protozoan Vaccines, Vaccines, Subunit, Antigens, Protozoan, Conserved Sequence, Time Factors, Complement System Proteins, Female
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 07 Jun 2021 09:48
Last Modified: 18 Oct 2023 05:33
DOI: 10.1038/s41586-021-03597-x
Open Access URL: https://www.biorxiv.org/content/10.1101/2021.02.10...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3125108