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

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.

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

“…The sIPV candidate had an acceptable safety profile and was able to stimulate potent increases in antibody titers in adults previously immunized with OPV, 17 supporting the assessment in infants reported here.…”

“…This dose-finding study in infants was initiated after the safety and immunogenicity of an initial formulation of the candidate vaccine with higher antigen content had been confirmed in adults. 17 A single dose of this vaccine was able to boost neutralizing antibody titers against both Salk and Sabin strains in adults previously vaccinated with OPV.…”

“… 12 Selection of vaccine doses was also based on the safety and immunogenicity of a higher dose vaccine administered in adults in a phase 1 clinical trial. 17 The D-antigen content of the sIPV formulations was determined using the cIPV standard reference, 31 as the sIPV international standard was not yet in use when trial enrollment began. The sIPV international standard was established by the World Health Organization (WHO) in November 2018.…”

“…31 The assays were performed at the Centers for Disease Control and Prevention (CDC, USA). Neutralizing antibodies against Salk or Sabin polioviruses were measured as previously described, 17 using the assay range till 10.5 Log 2 .…”

Circulation of Type 2 Vaccine-Derived Poliovirus in China in 2018–2019

“…During May 2016 to March 2021 after the switch, the Global Polio Laboratory Network had detected 1572 cases of cVDPV2, which were much higher than the 681 found in 2006–2016 in the world [ 3 ]. The number and geographic breadth of cVDPV2 outbreaks have exceeded the prediction of the World Health Organization (WHO) since the switch, and the probable reasons for this may be the following: (1) insufficient routine immunization coverage [ 4 ]; (2) the use of stored monovalent type 2 OPV(mOPV2) [ 5 ]; (3) the protracted cVDPV2 outbreaks from prior emergence have not been successfully controlled [ 6 ]; (4) circulating vaccine virus from previous vaccination with tOPV but low immunity against the type 2 from bOPV in the cohorts born after the switch [ 7 ]; (5) nucleotide substitutions at key neurovirulence determination sites and genetic rearrangements with human enterovirus C species et al [ 8 ].…”