Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trial

Abstract

Summary Background Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule. Methods This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at −10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov , NCT03239496 . Findings From Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95·9...

Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa

“…Routine delivery of two doses of IPV would provide substantially higher immunogenicity, especially in delayed schedules. 16,28 Our findings showing the additional role of IPV in preventing cVDPV2 paralysis contributed to the WHO recommendation in April, 2020 that all countries administering only one IPV dose in their routine immunisation schedule should introduce a second IPV dose in 2021−22. 25 Further analysis is needed to quantify the effects and cost-effectiveness of a second IPV dose.…”

Dose-Sparing Intradermal DTaP-sIPV Immunization With a Hollow Microneedle Leads to Superior Immune Responses

“…According to multiple clinical studies on ID immunity of fractional doses of cIPV ( Snider et al, 2019 ; Bandyopadhyay et al, 2021 ), ID immunization with two doses of 1/5 dose of cIPV can induce the same levels of NAbs as full-dose IM immunization. In the present study, immunization with the 1/5 dose of DTaP-sIPV ID induced the same levels of DTaP-related antibodies and poliovirus NAbs as IM immunization.…”

Safeguarding vaccine production and supply strategies for polio eradication endgame

“…The tradeoffs across delayed, dose sparing schedules with cost and supply advantages have to be carefully balanced out with any potential risk of vulnerability of young infants from ongoing polio transmission in high-risk areas. Non-inferiority of delayed, SAGE recommended schedules of Salk IPV -either in full or fractional doses -have also been demonstrated in randomized controlled trials [7] . Thus, the data presented by Zhijie An and colleagues help generate a comprehensive evidence base around novel schedules with different types of IPV formulations that are particularly relevant for policy formulation for immunization schedules in the post-OPV cessation era.…”