title: Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial.
abstract: BACKGROUND
  Intestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV.
  
  
  METHODS
  We did an open-label, randomised controlled trial in children aged 1-4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1:1) to receive 0·5 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005.
  
  
  RESULTS
  Between Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vaccine group (risk ratio 0·62, 95% CI 0·40-0·97, p=0·0375; 0·30, 0·18-0·49, p<0·0001). No adverse events were related to the study interventions.
  
  
  CONCLUSIONS
  The substantial boost in intestinal immunity conferred by a supplementary dose of IPV given to children younger than 5 years who had previously received OPV shows a potential role for this vaccine in immunisation activities to accelerate eradication and prevent outbreaks of poliomyelitis.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jacob
authors.initials: J
authors.lastname: John
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Sidhartha
authors.initials: S
authors.lastname: Giri
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Arun S
authors.initials: AS
authors.lastname: Karthikeyan
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Miren
authors.initials: M
authors.lastname: Iturriza-Gomara
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Muliyil
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India; Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address: n.grassly@imperial.ac.uk.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Grassly
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D007273:Injections, Intramuscular; D007422:Intestines / Q000276:immunology; D008297:Male; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D017201:Virus Shedding / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D011054:Poliovirus Vaccine, Inactivated; D011055:Poliovirus Vaccine, Oral