title: Shedding of sabin poliovirus Type 3 containing the nucleotide 472 uracil-to-cytosine point mutation after administration of oral poliovirus vaccine.
abstract: A uracil-to-cytosine point mutation at nucleotide (nt) 472 of Sabin oral poliovirus vaccine (OPV) type 3 is found in conjunction with vaccine-associated paralytic poliomyelitis (VAPP). Direct RNA extraction and mutant analysis by polymerase chain reaction and restriction enzyme cleavage were used to identify this point mutation in clinical samples. A total of 238 stool samples were obtained from 28 healthy infants for 6 weeks after OPV vaccination. More than 25% of infants shed OPV3 in the week after vaccination, with a decrease on day 6. A second wave of OPV3 shedding occurred beginning the second week after vaccination and was maintained through the end of the study period. During the first week after vaccination, the proportion of nt 472 mutants in the shed OPV3 increased from undetectable to almost 100%. During the second shedding period, the proportion of nt 472 mutants remained close to 100%. These results suggest that selective mutation drives the VAPP-associated nt 472 point mutation for OPV3 in the human gastrointestinal tract.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Martinez
authors.forename: Matt O
authors.initials: MO
authors.lastname: Old
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Kwock
authors.forename: Shalla S
authors.initials: SS
authors.lastname: Khan
authors.forename: Joaquin J
authors.initials: JJ
authors.lastname: Garcia
authors.forename: Christina S
authors.initials: CS
authors.lastname: Chan
authors.forename: Ramothea
authors.initials: R
authors.lastname: Webster
authors.forename: Meira S
authors.initials: MS
authors.lastname: Falkovitz-Halpern
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Maldonado
mesh_terms: D001483:Base Sequence; D005243:Feces / Q000821:virology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D017955:Poliovirus / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage*; D012367:RNA, Viral / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012641:Selection, Genetic; D014774:Virulence / Q000235:genetics; D017201:Virus Shedding
chemical_list: D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral