title: Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study.
abstract: OBJECTIVE
  Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV).
  
  
  METHODS
  Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice.
  
  
  RESULTS
  Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation.
  
  
  CONCLUSIONS
  Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852-1448, USA. dragunsky@cber.fda.gov
authors.forename: Eugenia
authors.initials: E
authors.lastname: Dragunsky
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nomura
authors.forename: Kazimir
authors.initials: K
authors.lastname: Karpinski
authors.forename: John
authors.initials: J
authors.lastname: Furesz
authors.forename: David J
authors.initials: DJ
authors.lastname: Wood
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pervikov
authors.forename: Shinobu
authors.initials: S
authors.lastname: Abe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurata
authors.forename: Olivier
authors.initials: O
authors.lastname: Vanloocke
authors.forename: Galina
authors.initials: G
authors.lastname: Karganova
authors.forename: Rolf
authors.initials: R
authors.lastname: Taffs
authors.forename: Alan
authors.initials: A
authors.lastname: Heath
authors.forename: Anna
authors.initials: A
authors.lastname: Ivshina
authors.forename: Inessa
authors.initials: I
authors.lastname: Levenbook
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000821:virology*; D003299:Cooperative Behavior; D005260:Female; D007753:Laboratories; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017955:Poliovirus / Q000276:immunology / Q000472:pathogenicity*; D011055:Poliovirus Vaccine, Oral / Q000633:toxicity*; D012680:Sensitivity and Specificity; D014774:Virulence; D014944:World Health Organization
chemical_list: D011055:Poliovirus Vaccine, Oral