title: 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.
authors.affiliation: Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Sawang
authors.initials: S
authors.lastname: Kesdangsakonwut
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sunden
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoshima
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okumura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
mesh_terms: D000818:Animals; D007114:Immunization / Q000401:mortality / Q000639:trends*; D007278:Injections, Spinal; D011817:Rabbits; D011818:Rabies / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011819:Rabies Vaccines / Q000008:administration & dosage*; D011820:Rabies virus / Q000187:drug effects*; D015996:Survival Rate / Q000639:trends
chemical_list: D011819:Rabies Vaccines
keywords: CNS pathology; animal experiment; intrathecal immunization; rabies virus; treatment of rabies