A Monoclonal Antibody-Based Therapy Against CNS-Resident Lyssavirus Infection
Abstract
Australian bat lyssavirus (ABLV) is a recently identified rabies-like virus that causes fatal disease in humans and horses. Clinical disease in humans is identical to that of rabies with individuals experiencing symptoms such as ataxia, muscle spasms, difficulty swallowing, paralysis, and encephalitis. Lyssavirus infection is thought to be universally fatal following central nervous system (CNS) involvement, and there are no effective therapies for rabies infections beyond clinical disease onset. In this study, we evaluated the therapeutic efficacy of F11, an anti-lyssavirus human monoclonal antibody (mAb), on established lyssavirus infection in mice. Via longitudinal tracing of lyssavirus infection in a mouse model of lethal disease, we found that a single dose of F11 mAb clears ABLV or rabies infections, even after onset of symptoms and demonstrable CNS involvement. Clearance depends on the host adaptive immune response, with CD4 T cells serving as the primary effector population. These preclinical data thus offer compelling evidence that human infections with rabies and related lyssaviruses may be treatable during the post-symptomatic stage of infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 19, 2018
- Accession Number
- AD1128492
Entities
People
- Kate E. Mastraccio
Organizations
- Uniformed Services University of the Health Sciences