Safety and immunogenicity of a new Sabin inactivated poliovirus vaccine candidate produced on the PER.C6® cell-line: a phase 1 randomized controlled trial in adults

Isabel Leroux-Roels, Geert Leroux-Roels, Georgi Shukarev, Hanneke Schuitemaker, Conor Cahill, Richard de Rooij, Martin Struijs, Hester van Zeeburg, Jeanne-Marie Jacquet, Isabel Leroux-Roels, Geert Leroux-Roels, Georgi Shukarev, Hanneke Schuitemaker, Conor Cahill, Richard de Rooij, Martin Struijs, Hester van Zeeburg, Jeanne-Marie Jacquet

Abstract

This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on the high-yield PER.C6® cell line. Healthy adults (N = 32) were randomized (1:1) to receive a single dose of PER.C6-based Sabin-IPV (sIPV, 15:35:112.5 DU/dose) or conventional Salk-IPV (cIPV, 40:8:32 DU/dose). Reactogenicity was assessed up to 7 days after vaccination, immunogenicity 28 days after vaccination, and safety up to 6 months after vaccination.Solicited adverse events (AEs) were mild to moderate, no changes of concern in vital signs or safety laboratory values were observed, and no severe AEs (SAEs) or vaccine-related unsolicited AEs were reported after vaccination. A trend to more frequent solicited AEs after sIPV than after cIPV administration was observed. Most participants had preexisting neutralizing antibodies against poliovirus types (titer ≥8), which were strongly boosted by sIPV. Post-vaccination geometric mean titers were high (≥12,000) and similar across the two vaccination groups. Only participants with very high preexisting antibody levels did not show a vaccine-induced response, defined in seropositive participants as a 4-fold titer increase. The 10 initially seronegative (titer <8) participants (n = 5 in each study group) seroconverted and all participants had seroprotective antibody levels post-vaccination. The antibodies elicited by sIPV neutralized both Sabin and Salk poliovirus strains.In conclusion, the PER.C6®-based sIPV was well tolerated and highly immunogenic in adults with preexisting antibodies to poliovirus.

Keywords: IPV; Inactivated; PER.C6; Sabin; poliovirus; vaccine.

Figures

Figure 1.
Figure 1.
Study disposition. cIPV = conventional Salk-IPV; sIPV = Sabin-IPV
Figure 2.
Figure 2.
Local and systemic solicited adverse events reported during the 7 days after vaccination. cIPV = conventional Salk-IPV; sIPV = Sabin-IPV
Figure 3.
Figure 3.
Geometric mean titers (with 95% CI) of poliovirus neutralizing antibodies before and after vaccination. Neutralizing titers to Salk (A) or Sabin (B) virus type 1, 2 and 3 are plotted for each group (n = 16 per group). Blue bars show the baseline titers of the subjects before vaccination, yellow bars the titers 28 days after vaccination. The lower limit of detection of the assay is 2, (6.49). Seroprotection in the Salk assay is a titer of 8 for each type 1, 2 and 3. Seroprotection titers for Sabin (type 1, 2 and 3) are not defined. cIPV = conventional Salk-IPV; CI = confidence interval; sIPV = Sabin-IPV
Figure 4.
Figure 4.
Reverse cumulative distribution curves of poliovirus neutralizing antibody titers against Salk strains before and 28 days after vaccination. Dotted line = before vaccination; Solid line = 28 days after vaccination. The vertical line at 2.7 shows the lower limit of quantitation of the assay. Red line = subjects who received sIPV; Blue line = subjects who received cIPV. cIPV = conventional Salk-IPV; sIPV = Sabin-IPV

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