Transgenic mice susceptible to poliovirus were recently produced by two groups of investigators (Ren et al., 1990: Koike et al., 1991). We compared the sensitivity of PVR Tg-1 mice and rhesus monkeys to poliovirus type 3, and it was 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) from those that failed. Unlike the monkey test which can detect as failed those vaccine lots which possess above one percent revertants at the 472 (U->C) position (Chumakov et al., 1991), the test in Tg-1 mice inoculated intracerebrally 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.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BR005003-03
Application #
3770473
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost