Abstract
Two phase 3 clinical studies were conducted in the USA to bridge across different Ad26.ZEBOV manufacturing processes and sites, and to evaluate the immunogenicity of different dose levels of Ad26.ZEBOV and MVA-BN-Filo. Study 1 evaluated the immunological equivalence of three batches of Ad26.ZEBOV administered as dose 1, followed by one batch of MVA-BN-Filo as dose 2. In Study 2, immunogenic non-inferiority of intermediate (Ad26.ZEBOV: 2 × 10(10) viral particles [vp], MVA-BN-Filo: 5 × 10(7) infectious units [Inf.U]) and low (8 × 10(9) vp, 5 × 10(7) Inf.U) doses of Ad26.ZEBOV and MVA-BN-Filo were evaluated against the full clinical dose (5 × 10(10) vp, 1 × 10(8) Inf.U). In Study 1, equivalence was demonstrated for two of three batch comparisons post-dose 1 and all three batches after the full regimen. Study 2 demonstrated a dose-dependent response; however, non-inferiority against the full clinical dose was not met. All regimens were well tolerated and immune responses were observed in all participants, regardless of manufacturing process or dose. Consistency of immunogenicity of different Ad26.ZEBOV batches was demonstrated and a dose-dependent response was observed after Ad26.ZEBOV, MVA-BN-Filo vaccination. ClinicalTrials.gov identifiers: NCT02543268; NCT02543567.