Safety and immunogenicity of 3 formulations of a Sabin inactivated poliovirus vaccine produced on the PER.C6® cell line: A phase 2, double-blind, randomized, controlled study in infants vaccinated at 6, 10 and 14 weeks of age

Abstract

An inactivated poliovirus vaccine candidate using Sabin strains (sIPV) grown on the PER.C6® cell line was assessed in infants after demonstrated immunogenicity and safety in adults. The study recruited 300 infants who were randomized (1:1:1:1) to receive one of 3 dose levels of sIPV or a conventional IPV based on Salk strains (cIPV). Poliovirus-neutralizing antibodies were measured before the first dose and 28 days after the third dose. Reactogenicity was assessed for 7 days and unsolicited adverse events (AEs) for 28 days after each vaccination. Serious AEs (SAEs) were recorded throughout the study. Solicited AEs were mostly mild to moderate. None of the SAEs reported in the study were judged vaccine related, including one fatal SAE due to aspiration of vomitus that occurred 26 days after the third dose of low-dose sIPV. After 3 sIPV vaccinations and across all dose levels, seroconversion (SC) rates were at least 92% against Sabin poliovirus types and at least 80% against Salk types, with a dose-response in neutralizing antibody geometric mean titers (GMTs) observed across the 3 sIPV groups. Compared to cIPV, the 3 sIPV groups displayed similar or higher SC rates and GMTs against the 3 Sabin types but showed a lower response against Salk types 1 and 2; this was most visible for Salk type 1. While the PER.C6® cell line-based sIPV showed an acceptable safety profile and immunogenicity in infants, lower seroprotection against type 1 warrants optimization of dose level and additional clinical evaluation.

Keywords: IPV; Inactivated; PER.C6® cell line; Sabin; infants; poliovirus; vaccine.

Figure 1.

Disposition of participants. Notes: IPV = inactivated polio vaccine; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV.

Figure 2.

Incidence of fever after 3-dose primary vaccination. The incidence of fever in categories as indicated in green, yellow, red, black and gray, after the 1^st, 2^nd and 3^rd immunization as well as the cumulative incidence, is shown for the different dose levels of sIPV and for cIPV. IPV = inactivated poliovirus vaccine; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV.

Figure 3.

Anti-poliovirus seroconversion rates (with 95% CI) 28 days after dose 3 – per protocol immunogenicity set. Seroconversion rates at 28 days after the 3^rd immunization for Salk and Sabin virus types 1, 2 and 3 are plotted for each group. Seroconversion was determined as described in the Methods. IPV = inactivated poliovirus vaccine; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV; CI = confidence interval.

Figure 4.

Anti-poliovirus seroprotection rates (with 95% CI) 28 days post-dose 3 – per protocol immunogenicity set. Seroprotection rates at 28 days after the 3^rd immunization for Salk and Sabin virus types 1, 2 and 3 are plotted for each group. Seroprotection was determined as described in the Methods. IPV = inactivated poliovirus vaccine; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV; CI = confidence interval.

Figure 5.

Anti-poliovirus geometric mean titers (with 95% CI) 28 days after dose 3 – per protocol immunogenicity set. Neutralizing antibody titers at 28 days after the 3^rd immunization for Salk and Sabin virus types 1, 2 and 3 are plotted as geometric mean titers for each group. Neutralizing antibody titers were determined as described in the Methods. IPV = inactivated poliovirus vaccine; GMT = geometric mean titer; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV; CI = confidence interval.

Figure 6.

Geometric mean poliovirus-neutralizing antibody titers (with 95% CI) 28 days post-dose 3 according to pre-vaccination serostatus–per protocol immunogenicity set. Neutralizing antibody titers at 28 days after the 3^rd immunization for Salk and Sabin virus types 1, 2 and 3 are plotted as geometric mean titers for each group for participants that were seronegative at baseline (open circles) or seropositive at baseline (full circles). Neutralizing antibody titers were determined as described in the Methods. IPV = inactivated poliovirus vaccine; sIPV = Sabin-IPV; LD = low dose; ID = intermediate dose; HD = high dose; cIPV = conventional Salk-IPV; CI = confidence interval; ULOQ, upper limit of quantification; SP = seroprotection threshold.