Highlights • A novel IPV vaccine was developed from attenuated Sabin poliovirus strains. • The vaccine was generally well tolerated in adults, toddlers and infants. • The vaccine was immunogenic as a booster in previously polio-vaccinated toddlers. • The vaccine was insufficiently immunogenic from 6 weeks of age in the EPI schedule. • There was evidence of interference of the immune response by maternal antibodies. Background To increase the global supply of affordable IPV vaccine, preferably using Sabin viruses to comply with GAPIII requirements, Takeda has assessed three dosages of a stand-alone sIPV. Methods In this phase I/II study two cohorts of 40 adults and 60 toddlers, respectively, were initially assessed for safety after receiving high -dosage sIPV compared with placebo (adults) or Salk IPV (toddlers). A cohort of 240 infants was then enrolled and randomized (1:1:1:1) to receive low -, medium – or high -dosage sIPV, or a reference Salk IPV in a three-dose primary schedule at 6, 10 and 14 weeks of age. Parents completed safety diaries for 4 weeks after each dose, and immunogenicity was measured as neutralization antibody titers at baseline and four weeks after vaccination. Results All vaccinations were generally well-tolerated and sIPV had a comparable safety profile to the control arm in adults or the reference Salk IPV vaccine in toddlers and infants. Infants displayed dosage-dependent immune responses to sIPV when assayed using Sabin strains, which were equivalent to the reference IPV in the high -dosage sIPV group for serotypes 1 and 2, but not for Sabin and Salk serotype 3. Seroconversion rates (SCR) of the low – and medium -dosage groups were significantly lower than the Salk IPV group for both Sabin and Salk serotypes 1 and type 2 (p < 0.05), with no significant differences for Salk or Sabin serotypes 3. Responses to sIPV, particularly to Sabin types 1 and 2, were higher in initially seronegative infants, indicating possible interference by maternally-derived antibodies. Conclusions A novel stand-alone Sabin-based IPV vaccine was well tolerated with an acceptable safety profile, but less immunogenic than reference Salk IPV at 6, 10 and 14 weeks of age for Salk serotypes 1 and 2, with apparent interference by maternal antibodies. Additional preclinical assessments will be made before any further clinical development.
【저자키워드】 Inactivated vaccine, Poliovirus, toddlers, Sabin, Infnats,