Inactivated polio vaccines from three different manufacturers have equivalent safety and immunogenicity when given as 1 or 2 additional doses after bivalent OPV: Results from a randomized controlled trial in Latin America

Eduardo Lopez-Medina,Mario Melgar,James T Gaensbauer,Ananda S Bandyopadhyay,Bhavesh R Borate,William C Weldon,Ricardo Rüttimann,Joel Ward,Ralf Clemens,Edwin J Asturias

doi:10.1016/j.vaccine.2017.04.041

Abstract

BackgroundSince April 2016 inactivated poliovirus vaccine (IPV) has been the only routine source of polio type 2 protection worldwide. With IPV supply constraints, data on comparability of immunogenicity and safety will be important to optimally utilize available supplies from different manufacturers. MethodsIn this multicenter phase IV study, 900 Latin American infants randomly assigned to six study groups received three doses of bOPV at 6, 10 and 14weeks and either one IPV dose at 14weeks (groups SP-1, GSK-1 and BBio-1) or two IPV doses at 14 and 36weeks (groups SP-2, GSK-2 and BBio-2) from three different manufacturers. Children were challenged with mOPV2 at either 18 (one IPV dose) or 40weeks (two IPV doses) and stools were collected weekly for 4weeks to assess viral shedding. Serum neutralizing antibodies were measured at various time points pre and post vaccination. Serious adverse events and important medical events (SAE and IME) were monitored for 6months after last study vaccine. ResultsAt week 18, 4weeks after one dose of IPV, overall type 2 seroconversion rates were 80.4%, 80.4% and 73.3% for SP-1, GSK-1 and BBio-1 groups, respectively; and 92.6%, 96.8% and 88.0% in those who were seronegative before IPV administration. At 40weeks, 4weeks after a second IPV dose, type 2 seroconversion rates were ≥99% for any of the three manufacturers. There were no significant differences in fecal shedding index endpoint (SIE) after one or two IPV doses (SP: 2.3 [95% CI: 2.1–2.6]); GSK: 2.2 [1.7–2.5]; BBio 1.8 [1.5–2.3]. All vaccines appeared safe, with no vaccine-related SAE or IME. ConclusionCurrent WHO prequalified IPV vaccines are safe and induce similar humoral and intestinal immunity after one or two doses.The parent study was registered with ClinicalTrials.gov, number NCT01831050.

Highlights

Since April 2016, all countries using OPV have switched to bivalent OPV as part of the final steps for global eradication of all-cause poliomyelitis. bOPV maintains protection against type 1 and 3 polioviruses, but leaves young children vulnerable to infection by type 2 vaccine-derived polioviruses [1,2]
With inactivated poliovirus vaccine (IPV) supply constraints, data on comparability of immunogenicity and safety will be important to optimally utilize available supplies from different manufacturers. In this multicenter phase IV study, 900 Latin American infants randomly assigned to six study groups received three doses of bOPV at 6, 10 and 14 weeks and either one IPV dose at 14 weeks or two IPV doses at 14 and 36 weeks from three different manufacturers
There were no significant differences in fecal shedding index endpoint (SIE) after one or two IPV doses (SP: 2.3 [95% CI: 2.1–2.6]); GSK: 2.2 [1.7– 2.5]; BBio 1.8 [1.5–2.3]

Summary

Introduction

Since April 2016, all countries using OPV have switched to bivalent OPV (bOPV) as part of the final steps for global eradication of all-cause poliomyelitis. bOPV maintains protection against type 1 and 3 polioviruses, but leaves young children vulnerable to infection by type 2 vaccine-derived polioviruses [1,2]. To strengthen population immunity and ensure all children are protected against type 2 polioviruses in countries that are polio-endemic or at high risk of importation of the virus, the WHO Strategic Advisory Group of Experts (SAGE) recommends at least one dose of IPV, given with the third dose of bOPV at 14 weeks of age or older to minimize interference from maternally-derived antibodies [3]. Universal IPV use will become routine to induce adequate type 2 protection, and to boost individual and population type 1 and 3 immunity in the final stages of global polio eradication. Results: At week 18, 4 weeks after one dose of IPV, overall type 2 seroconversion rates were 80.4%, 80.4% and 73.3% for SP-1, GSK-1 and BBio-1 groups, respectively; and 92.6%, 96.8% and 88.0% in those who were seronegative before IPV administration.

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Conclusion