A combination of two human monoclonal antibodies cures symptomatic rabies

• DOI: 10.15252/emmm.202012628
• Publication Date: 2020-09-18T09:03:11Z
• Authors: Guilherme Dias de...; Florian Sonthonnax; Gabriel Lepousez; Grégory Jouvion; Andrea Minola; Fabrizia Zatta; Florence Larrous; Lauriane Kergoat; Camille Mazo; Carine Moigneu; Roberta Aiello; Angela Salomoni; Elise Brisebard; Paola De Benedictis; Davide Corti; Hervé Bourhy
• Keywords: Medicine (General); Rabies; rabies virus Subject Categories Immunology; QH426-470; Antibodies, Viral; Microbiology; Mice; 03 medical and health sciences; R5-920; Dogs; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; neglected diseases; Genetics; Animals; Humans; rabies virus; 0303 health sciences; monoclonal antibody therapy; Antibodies, Monoclonal; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy; Articles; Antibodies, Neutralizing; neuroinfectious diseases; 3. Good health; Virology & Host Pathogen Interaction; immunotherapeutics; Rabies Vaccines; Rabies virus; [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases; Lyssavirus; [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy; Post-Exposure Prophylaxis

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.