Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial
© 2022. The Author(s), under exclusive licence to Springer Nature Limited..
Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-blind placebo-controlled phase of ENSEMBLE, an international randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titre as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; P = 0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID50 (<2.7 IU50 ml-1) and increased to 89% (78%, 96%) at ID50 = 96.3 IU50 ml-1. Comparison of the vaccine efficacy by ID50 titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID50 titre as a correlate of protection across trials and vaccine types.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Nature microbiology - 7(2022), 12 vom: 01. Dez., Seite 1996-2010 |
| Sprache: |
Englisch |
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| Anmerkungen: |
Date Completed 02.12.2022 Date Revised 13.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT04505722 UpdateOf: medRxiv. 2022 Apr 12;:. - PMID 35441174 Citation Status MEDLINE |
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| doi: |
10.1038/s41564-022-01262-1 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348712979 |
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| 245 | 1 | 0 | |a Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial |
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| 500 | |a Date Revised 13.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04505722 | ||
| 500 | |a UpdateOf: medRxiv. 2022 Apr 12;:. - PMID 35441174 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s), under exclusive licence to Springer Nature Limited. | ||
| 520 | |a Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-blind placebo-controlled phase of ENSEMBLE, an international randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titre as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; P = 0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID50 (<2.7 IU50 ml-1) and increased to 89% (78%, 96%) at ID50 = 96.3 IU50 ml-1. Comparison of the vaccine efficacy by ID50 titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID50 titre as a correlate of protection across trials and vaccine types | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
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| 700 | 1 | |a Castro, Mike |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Petropoulos, Christos J |e verfasserin |4 aut | |
| 700 | 1 | |a Luedtke, Alex |e verfasserin |4 aut | |
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| 700 | 1 | |a Kenny, Avi |e verfasserin |4 aut | |
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| 700 | 1 | |a Maboa, Rebone |e verfasserin |4 aut | |
| 700 | 1 | |a Randhawa, April K |e verfasserin |4 aut | |
| 700 | 1 | |a Andrasik, Michele P |e verfasserin |4 aut | |
| 700 | 1 | |a Hendriks, Jenny |e verfasserin |4 aut | |
| 700 | 1 | |a Truyers, Carla |e verfasserin |4 aut | |
| 700 | 1 | |a Struyf, Frank |e verfasserin |4 aut | |
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| 700 | 1 | |a Douoguih, Macaya |e verfasserin |4 aut | |
| 700 | 1 | |a Kublin, James G |e verfasserin |4 aut | |
| 700 | 1 | |a Corey, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Neuzil, Kathleen M |e verfasserin |4 aut | |
| 700 | 1 | |a Carpp, Lindsay N |e verfasserin |4 aut | |
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| 700 | 1 | |a Koup, Richard A |e verfasserin |4 aut | |
| 700 | 1 | |a Donis, Ruben O |e verfasserin |4 aut | |
| 700 | 0 | |a Immune Assays Team |e verfasserin |4 aut | |
| 700 | 0 | |a the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team |e verfasserin |4 aut | |
| 700 | 0 | |a and the United States Government (USG)/CoVPN Biostatistics Team |e verfasserin |4 aut | |
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