Nanobodies as antivirals against rabies in experimentally infected mice

ABSTRACT Despite its 100% lethality and approximately 59,000 human deaths every year, rabies still lacks an effective treatment. Numerous trials have aimed to impair the life cycle of Lyssavirus rabies (RABV), the primary worldwide lyssavirus causing rabies, but with limited success. Treatments targeting host factors and attempting to mitigate the damage caused by RABV have also been unsatisfactory. This article describes the effects of intracerebral transfection of anti-RABV recombinant monoclonal nanobodies as antivirals against rabies in vivo, in a post-exposure protocol. Mice were intranasally inoculated with the RABV CVS strain and, 72 h later, were injected via the intracerebral route with two different anti-RABV llama-derived VHH nanobodies complexed with a transfection agent. One of the VHHs was able to reduce the viral load in mice, but no significant effect on survival was detected. Though not completely effective, nanobody therapy could be attempted in association with other antivirals to improve therapies against rabies.