Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, compared to standard IPV: A phase 3 observer-blinded, randomised, controlled trial in infants vaccinated at 6, 10, 14 weeks and 9 months of age

Abstract

Background: A dose-sparing inactivated polio vaccine (IPV-Al), obtained by adsorption of inactivated virus to an aluminium hydroxide adjuvant, can help mitigate global supply and the cost constraints of IPV. The objective of this trial was to demonstrate the non-inferiority of IPV-Al to standard IPV.

Methods: This phase 3, observer-blinded, randomised, controlled trial was conducted at 5 investigational sites in the Philippines. Infants not previously vaccinated with any polio vaccines were randomised to receive three IPV-Al (n = 502) or IPV vaccinations (n = 500) at 6, 10 and 14 weeks of age plus a booster vaccination at 9 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series.

Results: Seroconversion rates following primary vaccination with IPV-Al (483 infants in the per-protocol analysis set) or IPV (478 infants) were: polio type 1, 97.1% versus 99.0%; type 2, 94.2% versus 99.0%; and type 3, 98.3% versus 99.6%. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the predefined -10%-point limit: type 1, -1.85% (-3.85; -0.05); type 2, -4.75% (-7.28; -2.52); type 3, -1.24 (-2.84; 0.13). The booster effect (geometric mean titre (GMT) post-booster / GMT pre-booster) was: type 1, 63 versus 43; type 2, 54 versus 47; type 3, 112 versus 80. IPV-Al was well tolerated with a safety profile comparable to that of IPV. Serious adverse events were recorded for 29 infants (5.8%, 37 events) in the IPV-Al group compared to 28 (5.6%, 48 events) in the IPV group.

Conclusion: Non-inferiority of IPV-Al to IPV with respect to seroconversion was confirmed and a robust booster response was demonstrated. Both vaccines had a similar safety profile. ClinicalTrials.gov identifier: NCT03032419.

Keywords: Affordable IPV; Aluminium hydroxide adjuvant; Booster vaccination; Immunogenicity; Polio; Primary vaccination.

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Birgit Thierry-Carstensen and Pernille Nyholm Tingskov are employees of Statens Serum Institut, a governmental non-profit research organization, and Charlotte Sørensen, Pernille Ingemann Nielsen and Mie Vestergaard Kusk are employees of AJ Vaccines A/S. Both Statens Serum Institut and AJ Vaccines A/S were involved in developing the vaccine at the time the trial was conducted. May Emmeline B. Montellano received research grants from Sanofi Pasteur and SK Chemicals. Ananda S. Bandyopadhyay is a full-time employee at the Bill & Melinda Gates Foundation].

Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1

Trial profile. Visit 4 was one month after the primary vaccination series at 14 weeks. Visit 6 was one month after the booster vaccination at 9 months. The full analysis set (FAS) was defined as all randomised and vaccinated infants with a valid primary endpoint for at least one poliovirus type. The per-protocol analysis set was defined as all infants in the FAS who had no major deviations from the protocol. The safety analysis set was defined as all randomised infants who received at least one treatment dose. N = number of infants in the group.

Fig. 2

Reverse cumulative antibody titre distribution curves at baseline (6 weeks), post-primary vaccination (18 weeks), pre-booster (9 months) and post-booster vaccination (10 months) for poliovirus type 1 (A), type 2 (B) and type 3 (C).