title: Immunogenicity of a new routine vaccination schedule for global poliomyelitis prevention: an open-label, randomised controlled trial.
abstract: BACKGROUND
  Polio eradication needs a new routine immunisation schedule--three or four doses of bivalent type 1 and type 3 oral poliovirus vaccine (bOPV) and one dose of inactivated poliovirus vaccine (IPV), but no immunogenicity data are available for this schedule. We aimed to assess immunogenicity of this vaccine schedule.
  
  
  METHODS
  We did an open-label, randomised controlled trial in four centres in India. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of five groups: trivalent OPV (tOPV); tOPV plus IPV; bOPV; bOPV plus IPV; or bOPV plus two doses of IPV (2IPV). The key eligibility criteria were: full-term birth (≥37 weeks of gestation); birthweight ≥2·5 kg; and Apgar score of 9 or more. OPV was administered at birth, 6 weeks, 10 weeks, and 14 weeks; IPV was administered intramuscularly at 14 weeks. The primary study objective was to investigate immunogenicity of the new vaccine schedule, assessed by seroconversion against poliovirus types 1, 2, and 3 between birth and 18 weeks in the per-protocol population (all participants with valid serology results on cord blood and at 18 weeks). Neutralisation assays tested cord blood and sera collected at 14 weeks, 18 weeks, 19 weeks, and 22 weeks by investigators masked to group allocation. This trial was registered with the India Clinical Trials Registry, number CTRI/2013/06/003722.
  
  
  RESULTS
  Of 900 newborn babies enrolled between June 13 and Aug 29, 2013, 782 (87%) completed the per-protocol requirements. Between birth and age 18 weeks, seroconversion against poliovirus type 1 in the tOPV group occurred in 162 of 163 (99·4%, 95% CI 96·6-100), in 150 (98·0%, 94·4-99·6) of 153 in the tOPV plus IPV group, in 153 (98·7%, 95·4-99·8) of 155 in the bOPV group, in 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and in 154 (99·4%, 96·5-100) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 2 occurred in 157 (96·3%, 92·2-98·6) of 163 in the tOPV group, 153 (100%, 97·6-100·0) of 153 in the tOPV plus IPV group, 29 (18·7%, 12·9-25·7) of 155 in the bOPV group, 107 (68·6%, 60·7-75·8) of 156 in the bOPV plus IPV group, and in 121 (78·1%, 70·7-84·3) of 155 in the bOPV plus 2IPV group. Seroconversion against poliovirus type 3 was achieved in 147 (90·2%, 84·5-94·3) of 163 in the tOPV group, 152 (99·3%, 96·4-100) of 153 in the tOPV plus IPV group, 151 (97·4%, 93·5-99·3) of 155 in the bOPV group, 155 (99·4%, 96·5-100) of 156 in the bOPV plus IPV group, and 153 (98·7%, 95·4-99·8) of 155 in the bOPV plus 2IPV group. Superiority was achieved for vaccine regimens including IPV against poliovirus type 3 compared with those not including IPV (tOPV plus IPV vs tOPV alone, p=0·0008; and bOPV plus IPV vs bOPV alone, p=0·0153). 12 serious adverse events occurred (six in the tOPV group, one in the tOPV plus IPV group, three in the bOPV group, zero in the bOPV plus IPV group, and two in the bOPV plus 2IPV group), none of which was attributed to the trial intervention.
  
  
  CONCLUSIONS
  The new vaccination schedule improves immunogenicity against polioviruses, especially against poliovirus type 3.
  
  
  BACKGROUND
  WHO, through a grant from Rotary International (grant number 59735).
authors.affiliation: World Health Organization, Geneva, Switzerland. Electronic address: sutterr@who.int.
authors.forename: Roland W
authors.initials: RW
authors.lastname: Sutter
authors.affiliation: World Health Organization, India-National Polio Surveillance Project, New Delhi, India; World Health Organization, Regional Office for South East Asia, New Delhi, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bahl
authors.affiliation: Enterovirus Research Center, Haffkine Institute Compound, Parel, Mumbai, India.
authors.forename: Jagadish M
authors.initials: JM
authors.lastname: Deshpande
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Harish
authors.initials: H
authors.lastname: Verma
authors.affiliation: World Health Organization, India-National Polio Surveillance Project, New Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Andhra Medical College, Visakhapatnam, India.
authors.forename: P
authors.initials: P
authors.lastname: Venugopal
authors.affiliation: Gandhi Medical College and Hospital, Secunderabad, India.
authors.forename: J Venkateswara
authors.initials: JV
authors.lastname: Rao
authors.affiliation: Dr D Y Patil Medical College, Pimpri, Pune, India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Agarkhedkar
authors.affiliation: Bharati Vidyapeeth Deemed University Medical College, Pune, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Lalwani
authors.affiliation: World Health Organization, India-National Polio Surveillance Project, New Delhi, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: World Health Organization, India-National Polio Surveillance Project, New Delhi, India.
authors.forename: Raman
authors.initials: R
authors.lastname: Sethi
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Marina
authors.initials: M
authors.lastname: Takane
authors.affiliation: Panacea Biotec Ltd, New Delhi, India.
authors.forename: Lalitendu
authors.initials: L
authors.lastname: Mohanty
authors.affiliation: Panacea Biotec Ltd, New Delhi, India; Biological E Ltd, Hyderabad, India.
authors.forename: Arani
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: T Jacob
authors.initials: TJ
authors.lastname: John
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Hamid
authors.initials: H
authors.lastname: Jafari
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Aylward
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D060740:Disease Eradication / Q000379:methods; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007231:Infant, Newborn; D008297:Male; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000069078:Seroconversion / Q000502:physiology; D014611:Vaccination / Q000379:methods
chemical_list: D000914:Antibodies, Viral; D007155:Immunologic Factors; D011054:Poliovirus Vaccine, Inactivated; D011055:Poliovirus Vaccine, Oral