TgPVR21 mice for testing type-3 oral poliovirus vaccines: role of clinical observation and histological examination.
Transgenic mice susceptible to poliovirus (TgPVR mice) have been used to study poliovirus neurovirulence and attenuation. It was shown recently that mouse line TgPVR21 may be a suitable model to evaluate neurovirulence safety of oral poliovirus vaccine. It was important to determine whether TgPVR21 mice are sensitive enough to discriminate between type-3 reference and 'marginal' vaccines, i.e. those that failed the monkey test while containing only slightly increased amounts of neurovirulent revertants at position 472 of the viral genome as measured by a molecular assay MAPREC. Data presented here demonstrate that TgPVR21 mice are not less sensitive than monkeys in the detection of marginal vaccines. In contrast to the monkey neurovirulence test, which is based on histological examination of the CNS, the TgPVR21 mouse neurovirulence test revealed marginal vaccines by simple analysis of clinical signs without requiring a laborious histological examination.
Dragunsky
E
E
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Chernokhvostova
Y
Y
Taffs
R
R
Chumakov
K
K
Gardner
D
D
Asher
D
D
Nomura
T
T
Hioki
K
K
Levenbook
I
I
D000818:Animals; D008253:Macaca mulatta; D051379:Mice; D008822:Mice, Transgenic / Q000502:physiology*; D011051:Poliomyelitis / Q000209:etiology / Q000473:pathology; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects*; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000473:pathology*; D014774:Virulence
D011055:Poliovirus Vaccine, Oral