Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, following vaccination in children at 2, 4, 6 and at 15-18 months

Abstract

Background: Availability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV.

Methods: A phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15-18 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. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0).

Results: Seroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined -10%-point limit: 3.94% (-6.51; -2.01) for type 1; 0.0% (-1.30; -1.37) for type 2; -0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV.

Conclusions: Non-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated. ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616.

Funding: Bill & Melinda Gates Foundation.

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

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Disclosures XSL and HW have no conflicts of interest to disclose. BTC and LSS are employees of Statens Serum Institut, a governmental non-profit research organisation. CS, PIN and MVK 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. ASB is a full-time employee at the Bill & Melinda Gates Foundation.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1

Disposition of subjects in the primary (A) and booster (B) trial. Fig. 1A. The full analysis set (FAS) defined as all randomised and vaccinated infants with at least one post-baseline measurement. The per-protocol (PP) analysis set was defined as all infants in the FAS who had no major deviations from the protocol. The safety analysis set (SAF) was defined as all randomised infants who received at least one treatment dose. N = number of infants in the group. *One subject completed but did not have a sample post-primary vaccination series and was excluded from FAS (hence FAS = 371). Fig. 1B. The full analysis set (FAS-booster) was defined as all enrolled subjects with the primary endpoint, i.e. the booster effect, for at least one of the three poliovirus types. The per-protocol analysis set (PP) was defined as all FAS subjects who did not have major deviations from the protocol. The safety analysis set (SAF) was defined as all enrolled subjects who received at least one trial vaccination. *Two subjects primed with IPV-Al did not have post-booster samples due to discontinuation and difficult venous access. ** Two subjects primed with IPV did not have post-booster samples due to discontinuation and difficult venous access.

Fig. 1

Disposition of subjects in the primary (A) and booster (B) trial. Fig. 1A. The full analysis set (FAS) defined as all randomised and vaccinated infants with at least one post-baseline measurement. The per-protocol (PP) analysis set was defined as all infants in the FAS who had no major deviations from the protocol. The safety analysis set (SAF) was defined as all randomised infants who received at least one treatment dose. N = number of infants in the group. *One subject completed but did not have a sample post-primary vaccination series and was excluded from FAS (hence FAS = 371). Fig. 1B. The full analysis set (FAS-booster) was defined as all enrolled subjects with the primary endpoint, i.e. the booster effect, for at least one of the three poliovirus types. The per-protocol analysis set (PP) was defined as all FAS subjects who did not have major deviations from the protocol. The safety analysis set (SAF) was defined as all enrolled subjects who received at least one trial vaccination. *Two subjects primed with IPV-Al did not have post-booster samples due to discontinuation and difficult venous access. ** Two subjects primed with IPV did not have post-booster samples due to discontinuation and difficult venous access.

Fig. 2

Geometric mean titres (GMTs) in infants primed with IPV-Al and IPV at baseline (2 months), post-primary vaccination (7 months), pre-booster (mean 16.5 months, range 15–18 months) and post-booster (mean 17.5 months, range 16–19 months) for poliovirus type 1 (A), type 2 (B) and type 3 (C). GMTs are shown as log2 values.

Fig. 3

Reverse cumulative titre distribution at baseline (2 months), post-primary vaccination (7 months), pre-booster (15–18 months) and post-booster (16–19 months) for poliovirus type 1 (A), type 2 (B) and type 3 (C). Subjects received either IPV-Al or IPV as primary vaccination; all subjects received IPV-Al as booster vaccination.