title: Genetic analysis and characterization of wild poliovirus type 1 during sustained transmission in a population with >95% vaccine coverage, Israel 2013.
abstract: BACKGROUND
  Israel has >95% polio vaccine coverage with the last 9 birth cohorts immunized exclusively with inactivated polio vaccine (IPV). Using acute flaccid paralysis and routine, monthly countrywide environmental surveillance, no wild poliovirus circulation was detected between 1989 and February 2013, after which wild type 1 polioviruses South Asia genotype (WPV1-SOAS) have persistently circulated in southern Israel and intermittently in other areas without any paralytic cases as determined by intensified surveillance of environmental and human samples. We aimed to characterize antigenic and neurovirulence properties of WPV1-SOAS silently circulating in a highly vaccinated population.
  
  
  METHODS
  WPV1-SOAS capsid genes from environmental and stool surveillance isolates were sequenced, their neurovirulence was determined using transgenic mouse expressing the human poliovirus receptor (Tg21-PVR) mice, and their antigenicity was characterized by in vitro neutralization using human sera, epitope-specific monoclonal murine anti-oral poliovirus vaccine (OPV) antibodies, and sera from IPV-immunized rats and mice.
  
  
  RESULTS
  WPV1 amino acid sequences in neutralizing epitopes varied from Sabin 1 and Mahoney, with little variation among WPV1 isolates. Neutralization by monoclonal antibodies against 3 of 4 OPV epitopes was lost. Three-fold lower geometric mean titers (Z = -4.018; P < .001, Wilcoxon signed-rank test) against WPV1 than against Mahoney in human serum correlated with 4- to 6-fold lower neutralization titers in serum from IPV-immunized rats and mice. WPV1-SOAS isolates were neurovirulent (50% intramuscular paralytic dose in Tg21-PVR mice: log10(7.0)). IPV-immunized mice were protected against WPV1-induced paralysis.
  
  
  CONCLUSIONS
  Phenotypic and antigenic profile changes of WPV1-SOAS may have contributed to the intense silent transmission, whereas the reduced neurovirulence may have contributed to the absence of paralytic cases in the background of high population immunity.
authors.affiliation: Public Health Services, Israel Ministry of Health, Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Lester M
authors.initials: LM
authors.lastname: Shulman
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Hertfordshire, United Kingdom.
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.affiliation: Public Health Services, Israel Ministry of Health, Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Danit
authors.initials: D
authors.lastname: Sofer
authors.affiliation: Polio and Picornavirus Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Cara C
authors.initials: CC
authors.lastname: Burns
authors.affiliation: Public Health Services, Israel Ministry of Health, Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Manor
authors.affiliation: Public Health Services, Israel Ministry of Health, Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Musa
authors.initials: M
authors.lastname: Hindiyeh
authors.affiliation: World Health Organization EUROPE, Regional Polio Laboratory Network, Copenhagen, Denmark.
authors.forename: Eugene
authors.initials: E
authors.lastname: Gavrilin
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Hertfordshire, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wilton
authors.affiliation: Ministry of Health, Jerusalem, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Moran-Gilad
authors.affiliation: Ministry of Health, Jerusalem, Israel.
authors.forename: Ronni
authors.initials: R
authors.lastname: Gamzo
authors.affiliation: Public Health Services, Israel Ministry of Health, Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Mendelson
authors.affiliation: Ministry of Health, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Grotto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D036022:Capsid Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004783:Environmental Microbiology; D005243:Feces / Q000821:virology*; D005260:Female; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010641:Phenotype; D017955:Poliovirus / Q000145:classification* / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014774:Virulence; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins
keywords: environmental surveillance; neurovirulence; neutralizing antigenic epitopes; poliovirus receptor; wild type 1 poliovirus