Assessments of different batches and dose levels of a two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen

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 × 10¹⁰ viral particles [vp], MVA-BN-Filo: 5 × 10⁷ infectious units [Inf.U]) and low (8 × 10⁹ vp, 5 × 10⁷ Inf.U) doses of Ad26.ZEBOV and MVA-BN-Filo were evaluated against the full clinical dose (5 × 10¹⁰ vp, 1 × 10⁸ 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.