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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Human vaccines & immunotherapeutics - 20(2024), 1 vom: 31. März, Seite 2327747 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Goldstein, Neil [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/21645515.2024.2327747 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Goldstein, Neil |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lot-to-lot consistency, immunogenicity, and safety of the Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen |b A phase 3, randomized, double-blind, placebo-controlled trial |
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| 500 | |a Date Completed 26.03.2024 | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 650 | 7 | |a Ebola Vaccines |2 NLM | |
| 650 | 7 | |a smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic |2 NLM | |
| 650 | 7 | |a TU8J357395 |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Smallpox Vaccine |2 NLM | |
| 650 | 7 | |a Vaccines, Attenuated |2 NLM | |
| 700 | 1 | |a McLean, Chelsea |e verfasserin |4 aut | |
| 700 | 1 | |a Gaddah, Auguste |e verfasserin |4 aut | |
| 700 | 1 | |a Doua, Joachim |e verfasserin |4 aut | |
| 700 | 1 | |a Keshinro, Babajide |e verfasserin |4 aut | |
| 700 | 1 | |a Bus-Jacobs, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Hendriks, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Luhn, Kerstin |e verfasserin |4 aut | |
| 700 | 1 | |a Robinson, Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Douoguih, Macaya |e verfasserin |4 aut | |
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