Biomaterial Database

Development of a neurovirulent testing system for oral poliovirus vaccine with transgenic mice. 1997

I Levenbook, and T Nomura

Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland, USA.

Because only primates are susceptible to polioviruses, the neurovirulent safety and consistency of oral poliovirus vaccine (OPV) were assayed in the monkey neurovirulence test. After the development of transgenic (Tg) mice carrying the gene for human poliovirus receptor (PVR), the suitability of these mice to replace monkeys for OPV testing was evaluated. Two lines of Tg mice, TgPVR1 and TgPVR21, were tested. The TgPVR21 mice, inoculated in the spinal cord, were as sensitive as monkeys in discriminating between type-3 and type-2 OPV lots that had passed and those that had failed the monkey neurovirulence test. Results of the new molecular assay by polymerase chain reaction and restriction enzyme cleavage indicated that each OPV lot contained minuscule amounts of neurovirulent revertants in the viral genome. All type-3 OPV lots that failed the monkey neurovirulence test had higher percentages of 472-C revertants than did lots that passed this test. Analysis of multiple type-3 OPV lots also indicated a good correlation between the contents of 472-C revertants and results of the TgPVR21 mouse test. An overview of a significant set of data suggests that the TgPVR21 mouse model is suitable for the evaluation of type-3 and type-2 OPV. The necessity of the TgPVR mouse test for the neurovirulence of type-1 OPV, which is the most stable of the three Sabin strains, is under consideration.

UI	MeSH Term	Description	Entries
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
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
D009420	Nervous System	The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)	Nervous Systems,System, Nervous,Systems, Nervous
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
D011991	Receptors, Virus	Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.	Viral Entry Receptor,Viral Entry Receptors,Virus Attachment Factor,Virus Attachment Factors,Virus Attachment Receptor,Virus Attachment Receptors,Virus Entry Receptor,Virus Entry Receptors,Virus Receptor,Virus Receptors,Attachment Factor, Virus,Attachment Factors, Virus,Attachment Receptor, Virus,Attachment Receptors, Virus,Entry Receptor, Viral,Entry Receptor, Virus,Entry Receptors, Viral,Entry Receptors, Virus,Receptor, Viral Entry,Receptor, Virus,Receptor, Virus Attachment,Receptor, Virus Entry,Receptors, Viral Entry,Receptors, Virus Attachment,Receptors, Virus Entry
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
D013116	Spinal Cord	A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.	Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
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
D017955	Poliovirus	A species of ENTEROVIRUS which is the causal agent of POLIOMYELITIS in humans. Three serotypes (strains) exist. Transmission is by the fecal-oral route, pharyngeal secretions, or mechanical vector (flies). Vaccines with both inactivated and live attenuated virus have proven effective in immunizing against the infection.	Brunhilde Virus,Human poliovirus 1,Human poliovirus 2,Human poliovirus 3,Lansing Virus,Leon Virus,Poliovirus Type 1,Poliovirus Type 2,Poliovirus Type 3,Polioviruses