Abstract
Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.
Highlights
Rabies is an ancient neurological disease caused mainly by the rabies virus (RABV) and is almost invariably fatal once clinical symptoms develop
108.3 50% egg infective doses completely protecting dogs from challenge with a street RABV for more than a year [31]. These results demonstrated that an Newcastle Disease Virus (NDV)-vectored vaccine can be utilized to induce long-lasting systemic protective immunity against rabies in animals and humans in high-risk areas to control rabies infections
Another promising delivery method has been proposed by Kumar et al, who have demonstrated that a short 29-amino-acid peptide, derived from the RABV G protein, which binds to the acetylcholine receptor exclusively expressed by neuronal cells, enables the transvascular delivery of small interfering RNAs (siRNAs) across the blood–brain barrier (BBB) to the brain [132]
Summary
Rabies is an ancient neurological disease caused mainly by the rabies virus (RABV) and is almost invariably fatal once clinical symptoms develop. The current PEP schedule requires multiple injections but is time-consuming, a problem that is even more pronounced due to the fact that RABV-specific immunoglobulin (RIG), which is both expensive and often in short supply, is required to treat severe exposure This creates a particular burden for rural regions of developing countries that suffer from the highest incidence rates of rabies. This review places particular emphasis on the most promising approaches using live-attenuated and/or recombinant vaccine platforms for preventive vaccinations Other innovative modalities, such as monoclonal antibody-based platforms and small interfering RNAs (siRNAs) interfering with virus replication, which may deserve future research for rabies treatment, will be briefly introduced
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