Related Experiment Videos
Transgenic PVR Tg-1 mice for testing of poliovirus type 3 neurovirulence: comparison with monkey test
E Dragunsky1, D Gardner, R Taffs
1Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Abstract:
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.
Insights
Transgenic mice can distinguish poliovirus strains but fail to identify unsafe vaccine lots. This poliovirus receptor (PVR) transgenic mouse model is not suitable for vaccine neurovirulence testing.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Poliovirus receptor (PVR) transgenic mice offer a new model for poliovirus research.
- Assessing the neurovirulence of poliovirus vaccines is critical for public health.
Purpose of the Study:
- To compare the sensitivity of PVR Tg-1 transgenic mice and rhesus monkeys in detecting poliovirus neurovirulence.
- To evaluate the suitability of the PVR Tg-1 mouse model for poliovirus vaccine safety testing.
Main Methods:
- Intracerebral inoculation of PVR Tg-1 mice and rhesus monkeys with poliovirus type 3 strains.
- Comparison of Tg-1 mouse and monkey responses to wild-type, attenuated, and vaccine revertant poliovirus strains.
- Analysis of the PVR Tg-1 mouse model's ability to detect revertant viruses in vaccine lots.
Main Results:
- PVR Tg-1 mice differentiated wild-type from attenuated poliovirus strains and vaccine revertants after intracerebral inoculation.
- The Tg-1 mouse model failed to discriminate between safe and unsafe live poliovirus vaccine lots, unlike the rhesus monkey test.
- Tg-1 mice did not detect revertant viruses at levels (3%) that would cause vaccine lots to fail the WHO-recommended monkey neurovirulence test (≥1%).
Conclusions:
- The PVR Tg-1 intracerebral mouse model is valuable for virological and epidemiological studies of poliovirus.
- This mouse model is not suitable for neurovirulence testing of live poliovirus vaccines.
- Alternative inoculation routes, such as intraspinal, in PVR transgenic mice may offer improved sensitivity for vaccine safety assessment.