Abstract : Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post-exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case-fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of anti-bodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody-based therapeutic approach for symptomatic rabies.
https://hal-pasteur.archives-ouvertes.fr/pasteur-02983042 Contributor : Guilherme Dias de MeloConnect in order to contact the contributor Submitted on : Thursday, October 29, 2020 - 11:22:37 AM Last modification on : Thursday, April 7, 2022 - 1:58:18 PM Long-term archiving on: : Saturday, January 30, 2021 - 6:16:02 PM
Guilherme Dias de Melo, Florian Sonthonnax, Gabriel Lepousez, Grégory Jouvion, Andrea Minola, et al.. A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO Molecular Medicine, Wiley Open Access, 2020, pp.e12628. ⟨10.15252/emmm.202012628⟩. ⟨pasteur-02983042⟩