title: Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial.
abstract: BACKGROUND
  Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV).
  
  
  METHODS
  We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429.
  
  
  RESULTS
  900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions.
  
  
  CONCLUSIONS
  The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3.
  
  
  BACKGROUND
  GAVI Alliance, World Health Organization, and Panacea Biotec.
authors.affiliation: World Health Organization, Geneva, Switzerland. sutterr@who.int
authors.forename: Roland W
authors.initials: RW
authors.lastname: Sutter
authors.forename: T Jacob
authors.initials: TJ
authors.lastname: John
authors.forename: Hemant
authors.initials: H
authors.lastname: Jain
authors.forename: Sharad
authors.initials: S
authors.lastname: Agarkhedkar
authors.forename: Padmasani Venkat
authors.initials: PV
authors.lastname: Ramanan
authors.forename: Harish
authors.initials: H
authors.lastname: Verma
authors.forename: Jagadish
authors.initials: J
authors.lastname: Deshpande
authors.forename: Ajit Pal
authors.initials: AP
authors.lastname: Singh
authors.forename: Meghana
authors.initials: M
authors.lastname: Sreevatsava
authors.forename: Pradeep
authors.initials: P
authors.lastname: Malankar
authors.forename: Anthony
authors.initials: A
authors.lastname: Burton
authors.forename: Arani
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Hamid
authors.initials: H
authors.lastname: Jafari
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Aylward
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005243:Feces / Q000821:virology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011051:Poliomyelitis / Q000517:prevention & control; D017955:Poliovirus / Q000276:immunology* / Q000302:isolation & purification; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D011055:Poliovirus Vaccine, Oral