First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age

Abstract

Background: There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans.

Methods: 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority.

Immunogenicity results: The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial.

Safety results: No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447.

Keywords: Affordable IPV; Aluminium hydroxide adjuvant; Dose investigation; IPV dose sparing.

Fig. 1

Disposition of subjects. The safety analysis set (SAF) was defined as randomised subjects who received a trial vaccination. The full analysis set (FAS) was defined as subjects who received a trial vaccination and had a post baseline immunogenicity measurement. The per protocol population (PP) was defined as the FAS with no major protocol deviations. All 240 subjects were included in the SAF, FAS and PP.

Fig. 2

Scatter plots of poliovirus type 1 antibody log 2(titres) for 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al and the comparator IPV Vaccine SSI. The post-vaccination log 2(titre) of the individual subjects are plotted on the y-axis versus the pre-vaccination log 2(titre) on the x-axis. The seroprotection cut-off level (a titre ⩾ 8) in normal scale corresponds to a log 2(titres) ⩾ 3.

Fig. 3

Scatter plots of poliovirus type 2 antibody log 2(titres) for 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al and the comparator IPV Vaccine SSI. The post-vaccination log 2(titre) of the individual subjects are plotted on the y-axis versus the pre-vaccination log 2(titre) on the x-axis. The seroprotection cut-off level (a titre ⩾ 8) in normal scale corresponds to a log 2(titres) ⩾ 3.

Fig. 4

Scatter plots of poliovirus type 3 antibody log 2(titres) for 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al and the comparator IPV Vaccine SSI. The post-vaccination log 2(titre) of the individual subjects are plotted on the y-axis versus the pre-vaccination log 2(titre) on the x-axis. The seroprotection cut-off level (a titre ⩾ 8) in normal scale corresponds to a log 2(titres) ⩾ 3.