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.

Conflict of interest statement

Janssen Vaccines & Prevention B.V. was the clinical trial Sponsor and was involved in the design and conduct of the trial, and in the collection and analysis of data. V.B., A.G., N.G., G.S., K.L., C.R., D.A., M.L. and M.D. were full-time employees of Janssen, Pharmaceutical Companies of Johnson & Johnson at the time of the study, and may own shares in Janssen, Pharmaceutical Companies of Johnson & Johnson. SB reports grants from Janssen, Pharmaceutical Companies of Johnson & Johnson during the conduct of the study, paid to Optimal Research LLC.

© 2021. The Author(s).

Figures

Fig. 1. Study flow.

Panel a shows the study flow for Study 1. Panel b shows the study flow for Study 2. Inf.U: infectious units; MVS: master virus seed; vp: viral particles; WVS: working virus seed. *Same Leiden MVS batch as used in phase 1/2 studies.

Fig. 2. Geometric mean concentrations of EBOV-specific binding antibodies in the two studies.

Panel a (Study 1) shows the geometric mean profile of the three different batches of Ad26.ZEBOV (5 × 1010 vp) (Group 1: Leiden WVS, batch #33831; Group 2: Bern WVS, batch #33488; Group 3: Leiden MVS*, batch #32642), MVA-BN-Filo (1 × 108 Inf.U), or placebo, placebo (Group 4) administered 56 days apart. Panel b (Study 2) shows the geometric mean profile of the different dose levels - Group 1 (full clinical dose: Ad26.ZEBOV [5 × 1010 vp], MVA-BN-Filo [1 × 108 Inf.U]), Group 2 (intermediate dose: Ad26.ZEBOV [2 × 1010 vp], MVA-BN-Filo [5 × 107 Inf.U]), Group 3 (low dose: Ad26.ZEBOV [8 × 109 vp], MVA-BN-Filo [5 × 107 Inf.U]), or Group 4 (placebo, placebo), administered 56 days apart. Both panels show the change in geometric mean concentrations over time (for actual values, see Table 2). Error bars in both panels represent the 95% confidence intervals. Inf.U: infectious units; LLOQ: lower limit of quantification; MVS: master virus seed; vp: viral particles; WVS: working virus seed. *Same Leiden MVS batch as used in phase 1/2 studies.