Phase 2 trial to evaluate the safety and immunogenicity of a 25-valent pneumococcal conjugate vaccine (IVT-PCV25) in infants

Introduction IVT-PCV25 is a 25-valent pneumococcal conjugate vaccine designed to broaden serotype coverage beyond current vaccines. We evaluated the safety and immunogenicity in infants of three dose-ranging formulations of IVT-PCV25 in comparison to licensed Prevnar-20. Methods In this double-blind phase 2 trial in the Philippines, 421 healthy infants were randomly assigned (1:1:1:1) to three IVT - PCV25–formulation arms or a Prevnar-20 arm. Three doses were administered 4-weeks apart from 6 weeks of age, alongside routine vaccinations. Adverse events (AEs), and IgG and functional antibody (opsonophagocytic; OPA) titres were assessed up to 28-days after Dose 3. Unlike IgG concentrations, OPA titres were only measured in a third of the population. Results Solicited local and systemic AEs were reported for 90–93% and 94–99% of IVT - PCV25 recipients, respectively, and for 84% and 97% of Prevnar-20 recipients, respectively. These AEs were predominantly mild or moderate, and transient. No serious AE was attributed to IVT - PCV25. All formulations of IVT - PCV25 appeared immunogenic by IgG assay or OPA, or both. IgG GMTs to 19/25 serotype antigens were above the aggregate correlate-of-protection threshold of 0.35 μg/mL; and for the other 6/25 serotypes, the OPA GMTs were > 50-fold the lower limit of quantification (8 dil −1 ). No clear dose effect was observed. A 2-fold change in antigen quantity only led to a corresponding 2-fold antibody response for four serotypes, and by OPA only. In Prevnar-20 recipients, IgG GMCs were ≥ 0.85 μg/mL for all shared serotypes. Conclusions In infants, IVT - PCV25 had an acceptable safety profile. Although the results suggest that IVT-PCV25 has the potential to broaden serotype coverage, there is scope for formulation optimisation by rebalancing serotype-antigen quantities.