Lot-to-lot consistency, immunogenicity, and safety of the Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen: A phase 3, randomized, double-blind, placebo-controlled trial

ABSTRACT

This phase-3, double-blind, placebo-controlled study (NCT04228783) evaluated lot-to-lot consistency of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Participants were randomized (6:6:6:1) to receive the two-dose regimen from three consecutively manufactured lots of Ad26.ZEBOV on Day 1 paired with three consecutively manufactured lots of MVA-BN-Filo on Day 57 (Groups 1–3) or two doses of placebo (Group 4). An additional cohort also received an Ad26.ZEBOV booster or placebo 4 months post-dose 2. Equivalence of the immunogenicity at 21 days post-dose 2 between any two groups was demonstrated if the 95% confidence interval (CI) of the Ebola virus glycoprotein (EBOV GP)–binding antibody geometric mean concentration (GMC) ratio was entirely within the prespecified margin of 0.5–2.0. Lot-to-lot consistency (i.e., consecutive lots can be consistently manufactured) was accomplished if equivalence was shown for all three pairwise comparisons. Results showed that the primary objective in the per-protocol immunogenicity subset (n = 549) was established for each pairwise comparison (Group 1 vs 2: GMC ratio = 0.9 [95% CI: 0.8, 1.1], Group 1 vs 3: 0.9 [0.8, 1.1], Group 2 vs 3: 1.0 [0.9, 1.2]). Equivalence of the three groups for the Ad26.ZEBOV component only was also demonstrated at 56 days post-dose 1. EBOV GP–binding antibody responses (post-vaccination concentrations >2.5-fold from baseline) were observed in 419/421 (99.5%) vaccine recipients at 21 days post-dose 2 and 445/460 (96.7%) at 56 days post-dose 1. In the booster cohort (n = 39), GMCs increased 9.0- and 11.8-fold at 7 and 21 days post-booster, respectively, versus pre-booster. Ad26.ZEBOV, MVA-BN-Filo was well tolerated, and no safety issues were identified.

KEYWORDS:

• Ebola
• Ad26.ZEBOV
• MVA-BN-Filo
• vaccine
• immunogenicity
• clinical trial

Acknowledgments

The authors wish to acknowledge Chan Tang, of Janssen Vaccines & Prevention B.V., for contributions to this study. Medical writing support was provided by Michelle Hughes, of Lumanity Communications Inc., and was funded by Janssen Vaccines & Prevention B.V.

Disclosure statement

NG, JD, and MD were employees of Janssen at the time the study was conducted. CM, AG, BK, LB-J, JH, KL, and CR are current employees of Janssen. All authors are stockholders of Johnson & Johnson.

Author contributions statement

NG, AG, JD, JH, KL, CR, and MD were involved in the conception and design of the study. NG, CM, AG, JD, BK, LB-J, JH, KL, CR, and MD contributed to the analysis and interpretation of the data. NG, CM, AG, and JD contributed to drafting of the manuscript. All authors revised the manuscript critically for intellectual content, approved the final version to be published, and agree to be accountable for all aspects of the work.

Data availability statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access [YODA] Project site at http://yoda.yale.edu.

Prior presentation

The design and findings of this study were previously presented as a poster at the 16th Vaccine Congress, on 12–14 September 2022, at Lake Garda, Italy.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2327747.

Additional information

Funding

This study was sponsored by Janssen Vaccines & Prevention B.V.