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Abstract. Two poliovirus-susceptible transgenic mouse (Tg PVR) strains, Tg1 and Tg21, were compared with the monkey test for their sensitivity to neurovirulence of live oral poliovirus vaccine (OPV). Intracerebral (i.c.) and intraspinal (i.s.) routes of inoculation were investigated to determine the most suitable combination of mouse strain and route. Evaluation of the mouse tests was performed using several indicators; clinical score and failure time were selected as the most efficient. Tg1 and Tg21 mice inoculated i.s. with type 2, and Tg21 mice inoculated i.s. with type 3 OPV were determined to be the most appropriate systems, whereas they are shown not to be suitable for type 1 OPV. The sensitivity of each of the two mouse models was at least equal to that of the monkey test, suggesting that these mouse systems might be considered as a potential replacement for the monkey test of OPV. However, more data are needed to establish regulatory criteria of acceptability for vaccine lots tested in Tg PVR mice. This is the first study conducted with Tg PVR mice with all three types of poliovirus vaccine preparations.

Transgenic mice susceptible to poliovirus were recently produced by two groups of investigators. In this study, we compared the sensitivity of PVR Tg-1 transgenic mice and rhesus monkeys to poliovirus type 3. We found that intracerebrally inoculated Tg-1 mice are able to differentiate wild-type strain from attenuated strains and from a vaccine revertant. However, this mouse system can not discriminate between live poliovirus vaccine lots which passed the intraspinal (i.s.) monkey neurovirulence safety test (WHO) and those that failed. Unlike the monkey test which can detect as failed those vaccine lots which possess above 1% revertants at the 472 (U-->C) position, the test in Tg-1 mice inoculated intracerebrally (i.c.) did not recognize virus preparations containing even three percent revertants. Thus, the PVR Tg-1 i.c. mouse model is suitable for epidemiological and other virological studies, but it does not appear to be useful for neurovirulence testing of live poliovirus vaccines. A solution to the latter may be found in the use of a more sensitive i.s. route of inoculation of PVR Tg mice.