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 te sted in monkeys, because only primates are sensitive to all three types of poliovirus. The genetic engineering of transgenic mice susceptible to polio virus led to studies on the suitability of these mice for a neurovirulence test of OPV. A WHO international collaborative study started with type-3 OP V 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 l umbar cord, provided a test for neurovirulence of OPV as sensitive and repr oducible as the monkey test. A statistical decision model for acceptance/re jection of type-3 vaccines using the transgenic mouse test has been develop ed. The mouse neurovirulence test showed a number of essential advantages o ver the monkey lest. This is the first example of a successful introduction of transgenic animals into control of biologicals. In October 1999, the WH O Expert Committee on Biological Standardization approved TgPVR21 mice as a lternative to the monkey model for neurovirulence resting 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 product ion of TgPVR21 mice are being established in Asia and Europe. (C) 2000 Else vier Science Ltd. All rights reserved.