Safety and immunogenicity of inactivated poliovirus vaccineudwhen given with measles–rubella combined vaccine andudyellow fever vaccine and when given via diff erentudadministration routes: a phase 4, randomised, non-inferiority trial in The Gambia

摘要

Background The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the poliouderadication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles–rubellaudand yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe oruddisposable-syringe jet injector.udMethods We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia.udInfants aged 9–10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV,udmeasles–rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a fulludintramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit.udThe primary outcomes were seroprevalence rates for poliovirus 4–6 weeks post-vaccination and the rate ofudseroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and theudpost-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis withuda non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion,udand (⅓) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872.udFindings Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolledudinto one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route ofudadministration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversionudrates achieved non-inferiority in both cases (rubella, –4·5% [95% CI –9·5 to –0·1]; yellow fever, 1·2% [–2·9 to 5·5]).udMeasles and poliovirus responses were unaff ected (measles, 6·8% [95% CI –1·4 to 14·9]; poliovirus serotype 1, 1·6%ud[–6·7 to 4·7]; serotype 2, 0·0% [–2·1 to 2·1]; serotype 3, 0·0% [–3·8 to 3·9]). Poliovirus seroprevalence was universallyudhigh (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieveudnon-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres wasudalso lower by the intradermal route. There were no safety concerns.udInterpretation The data support the future co-administration of IPV, measles–rubella, and yellow fever vaccinesudwithin the Expanded Programme on Immunization schedule at 9 months. The administration of single fractionaludintradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunityudgenerated, although it results in a high post-vaccination poliovirus seroprevalence.