Transgenic PVR Tg-1 mice for testing of poliovirus type 3 neurovirulence: comparison with monkey test.
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.
Dragunsky
E
E
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Gardner
D
D
Taffs
R
R
Levenbook
I
I
D000818:Animals; D002490:Central Nervous System / Q000382:microbiology*; D008253:Macaca mulatta; D051379:Mice; D008822:Mice, Transgenic; D017955:Poliovirus / Q000472:pathogenicity*; D014765:Viral Vaccines; D017735:Virus Latency
D014765:Viral Vaccines