title: Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial.
abstract: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.
  
  
  
  Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.
  
  
  
  We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.
  
  
  
  Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.
authors.affiliation: Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Marya
authors.initials: M
authors.lastname: Carmolli
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Dadong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: E Ross
authors.initials: ER
authors.lastname: Colgate
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Nayak
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Mami
authors.initials: M
authors.lastname: Taniuchi
authors.affiliation: Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Dickson
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Weldon
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: M Steven
authors.initials: MS
authors.lastname: Oberste
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh.
authors.forename: K
authors.initials: K
authors.lastname: Zaman
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Houpt
authors.affiliation: Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh.
authors.forename: Masud
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. Electronic address: wap3g@virginia.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D001459:Bangladesh; D005243:Feces / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal; D007223:Infant; D011051:Poliomyelitis / Q000517:prevention & control*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D011054:Poliovirus Vaccine, Inactivated
keywords: ClinicalTrials.gov NCT01375647; Inactivated poliovirus vaccine; Intestinal immunity; Oral poliovirus vaccine; Poliomyelitis; Serum neutralizing antibody; Shedding