Development of a transgenic mouse neurovirulence test for oral poliovirus vaccine: international collaborative study 1993-1999.
The neurovirulence safety of oral live poliovirus vaccine (OPV) has been tested in monkeys, because only primates are sensitive to all three types of poliovirus. The genetic engineering of transgenic mice susceptible to poliovirus led to studies on the suitability of these mice for a neurovirulence test of OPV. A WHO international collaborative study started with type-3 OPV in 1993 and was completed in 1999. The study produced a voluminous set of data proving that the TgPVR21 mice, inoculated with OPV samples into the lumbar cord, provided a test for neurovirulence of OPV as sensitive and reproducible as the monkey test. A statistical decision model for acceptance/rejection of type-3 vaccines using the transgenic mouse test has been developed. The mouse neurovirulence test showed a number of essential advantages over the monkey test. This is the first example of a successful introduction of transgenic animals into control of biologicals. In October 1999, the WHO Expert Committee on Biological Standardization approved TgPVR21 mice as alternative to the monkey model for neurovirulence testing of OPV type 3. A final step of the collaborative study with OPV types 1 and 2 is in progress, and data obtained so far are promising. Two breeding stations for production of TgPVR21 mice are being established in Asia and Europe.
Levenbook
I
I
Center for Biological Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Dragunsky
E
E
Pervikovc
Y
Y
D000818:Animals; D002522:Chlorocebus aethiops; D051379:Mice; D008822:Mice, Transgenic; D011055:Poliovirus Vaccine, Oral / Q000633:toxicity*; D013997:Time Factors; D014709:Vero Cells; D014774:Virulence
D011055:Poliovirus Vaccine, Oral