title: Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.
abstract: Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days.
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan. Electronic address: mutsuito@nih.go.jp.
authors.forename: Mutsuyo
authors.initials: M
authors.lastname: Takayama-Ito
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Chang-Kweng
authors.initials: CK
authors.lastname: Lim
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamichi
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Kakiuchi
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Horiya
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Posadas-Herrera
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
mesh_terms: D000818:Animals; D001835:Body Weight / Q000276:immunology; D002642:Chick Embryo; D005260:Female; D006801:Humans; D051379:Mice; D011818:Rabies / Q000276:immunology* / Q000401:mortality / Q000821:virology; D011819:Rabies Vaccines / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology*; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D064166:Vaccine Potency; D015164:Vaccines, Inactivated / Q000276:immunology; D015431:Weight Loss / Q000276:immunology
chemical_list: D011819:Rabies Vaccines; D015164:Vaccines, Inactivated
keywords: Animal welfare; Humane endpoint; Inactivated rabies vaccine; Potency test; Reduction; Vaccine quality control