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 antibodies 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.
Highlights
Rabies is a lethal acute encephalomyelitis caused by a neurotropic Lyssavirus mainly transmitted to humans by the bite of domestic dogs (WHO, 2018)
In the quest for a novel therapeutic possibility, we have previously reported the selection of two human monoclonal antibodies, RVC20 and RVC58, that were able to bind to two distinct antigenic sites on the RABV glycoprotein protein, to potently neutralize RABV isolates of all lineages, and of all phylogroup I non-RABV isolates, and that presented a protective
Here, we established a protocol to treat symptomatic rabies in mice using a cocktail of two potent neutralizing human monoclonal antibodies
Summary
Rabies is a lethal acute encephalomyelitis caused by a neurotropic Lyssavirus mainly transmitted to humans by the bite of domestic dogs (WHO, 2018). We show that a combination of the RVC20 and RVC58 monoclonal antibodies can effectively cure already symptomatic mice (late infection) when concomitantly administered both directly in the central nervous system, through intracerebroventricular infusion, and in the periphery, at the site of the infection. After such treatment, mice that survived the infection presented good clinical condition, the viral load was absent, and the inflammatory profile in the brain was close to that of uninfected animals. Our findings provide proof of concept that a targeted administration of human monoclonal antibodies represents a possibility with an unprecedented breadth and potency for the development of a lowrisk product to treat rabies
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