Development of a transgenic mouse neurovirulence test for oral poliovirus vaccine: international collaborative study 1993-1999. 2000

I Levenbook, and E Dragunsky, and Y Pervikovc
Center for Biological Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.

The neurovirulence safety of oral live poliovirus vaccine (OPV) has been tested in monkeys, because only primates are sensitive to all three types of poliovirus. The genetic engineering of transgenic mice susceptible to poliovirus led to studies on the suitability of these mice for a neurovirulence test of OPV. A WHO international collaborative study started with type-3 OPV in 1993 and was completed in 1999. The study produced a voluminous set of data proving that the TgPVR21 mice, inoculated with OPV samples into the lumbar cord, provided a test for neurovirulence of OPV as sensitive and reproducible as the monkey test. A statistical decision model for acceptance/rejection of type-3 vaccines using the transgenic mouse test has been developed. The mouse neurovirulence test showed a number of essential advantages over the monkey test. This is the first example of a successful introduction of transgenic animals into control of biologicals. In October 1999, the WHO Expert Committee on Biological Standardization approved TgPVR21 mice as alternative to the monkey model for neurovirulence testing of OPV type 3. A final step of the collaborative study with OPV types 1 and 2 is in progress, and data obtained so far are promising. Two breeding stations for production of TgPVR21 mice are being established in Asia and Europe.

UI MeSH Term Description Entries
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011055 Poliovirus Vaccine, Oral A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed) Sabin Vaccine,Oral Poliovirus Vaccine,Vaccine, Oral Poliovirus,Vaccine, Sabin
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014709 Vero Cells A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays. Cell, Vero,Cells, Vero,Vero Cell
D014774 Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS. Pathogenicity
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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