Survival of rabid rabbits after intrathecal immunization

Abstract

Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4–8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8–12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11–18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies.

Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs

“…Similar IT vaccination in dogs has been reported by Baer et al, which not only induced VNA in the CSF, but also prolonged the morbidity [ 61 ]. Recent report of survival of rabid rabbits after IT immunization highlights the importance of CSF VNA on viral clearance [ 30 ]. Furthermore, it has recently been demonstrated that the RABV infection can be cleared from the CNS by exogenous administration of VNA in immunocompetent or immunocompromised mice, as long as the BBB permeability is enhanced for the passage of VNA from the periphery to the CNS [ 29 ].…”

“…It has been shown most recently that it is possible to clear an established infection with wt RABV by intravenous administration of VNA in both immunocompromised and immunocompetent mice as long as the BBB permeability is enhanced [ 29 ]. It has also been shown in rabid rabbits that it is possible to reverse the course of infection by intrathecal immunization with attenuated RABV [ 30 ].…”

Novel Approaches to the Prevention and Treatment of Rabies

“…Recently, it has been shown that the intrathecal inoculation of rabies vaccines directly into the CSF of rabbits showing neuromuscular symptoms of rabies, led to the clearance of RABV from the CNS and their survival [100]. Thus, these studies provide evidence of RBAV clearance from CNS and possible therapy for rabies using intrathecal RABV immunization.…”

29-kDa: A Potential Candidate for Anti-Tick Vaccine Antigen Source as Immunogenic and Stage Reactive Targeting Hard-Bodied Hyalomma Ticks Ixodidae

“…Red cell agglutination at  1:25 was considered positive for the presence of antibody (Harris et al 2009). White Rabbits weighing 3-4 kg were selected for positive and negative testing groups for the developed vaccine for its possible immunogenic reaction in horses (Kesdangsakonwut et al 2014).…”