Novel Approaches to the Prevention and Treatment of Rabies

Rabies is a highly lethal disease caused by the neurotropic rabies virus (RABV), and it remains an important public health problem globally. Effective vaccines have been developed for pre- and post-exposure prophylaxis (PEP). PEP is only effective if it is initiated promptly after recognizing exposure. Once neurological symptoms develop, however, it is widely accepted that there is no effective treatment available. Recent studies indicate that the presence of RABV-specific immunity (i.e. Virus neutralizing antibodies, VNA) and the transient enhancement of the BBB permeability are absolutely required for effective virus clearance from the CNS. In principle, it has been shown in mice using various live-attenuated RABVs or recombinant RABVs expressing three copies of the G or expressing chemokine/cytokines, which can induce high levels of VNA in the serum and also capable of transiently enhancing the BBB permeability that it is possible to clear the virus from CNS. Also, it has been demonstrated that, intravenous administration of VNA together with MCP-1 (shown to transiently open up BBB) can clear RABV from the CNS in both immunocompetent and immunocompromised mice, as late as 5 days after lethal challenge. Novel therapeutic approaches aimed at allowing the peripheral VNA to cross the BBB by administration of the VNA in combination with biological or chemical agents that can transiently open up the BBB would be useful to establish an effective therapy for rabies in humans. In this review, we focus on the some of the approaches that can be used to meet the challenges in the field of rabies treatment.