tetano
Editor, Senior Moderator
Nat Microbiol
. 2022 Nov 10.
doi: 10.1038/s41564-022-01262-1. Online ahead of print.
Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial
Youyi Fong[SUP] 1 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP], David Benkeser[SUP] 4 [/SUP], Sanne Roels[SUP] 5 [/SUP], Daniel J Stieh[SUP] 6 [/SUP], An Vandebosch[SUP] 5 [/SUP], Mathieu Le Gars[SUP] 6 [/SUP], Griet A Van Roey[SUP] 6 [/SUP], Christopher R Houchens[SUP] 7 [/SUP], Karen Martins[SUP] 7 [/SUP], Lakshmi Jayashankar[SUP] 7 [/SUP], Flora Castellino[SUP] 7 [/SUP], Obrimpong Amoa-Awua[SUP] 3 [/SUP], Manjula Basappa[SUP] 3 [/SUP], Britta Flach[SUP] 3 [/SUP], Bob C Lin[SUP] 3 [/SUP], Christopher Moore[SUP] 3 [/SUP], Mursal Naisan[SUP] 3 [/SUP], Muhammed Naqvi[SUP] 3 [/SUP], Sandeep Narpala[SUP] 3 [/SUP], Sarah O'Connell[SUP] 3 [/SUP], Allen Mueller[SUP] 3 [/SUP], Leo Serebryannyy[SUP] 3 [/SUP], Mike Castro[SUP] 3 [/SUP], Jennifer Wang[SUP] 3 [/SUP], Christos J Petropoulos[SUP] 8 [/SUP], Alex Luedtke[SUP] 9 [/SUP], Ollivier Hyrien[SUP] 1 2 [/SUP], Yiwen Lu[SUP] 1 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Bhavesh Borate[SUP] 1 [/SUP], Lars W P van der Laan[SUP] 1 9 [/SUP], Nima S Hejazi[SUP] 1 10 [/SUP], Avi Kenny[SUP] 11 [/SUP], Marco Carone[SUP] 11 [/SUP], Daniel N Wolfe[SUP] 7 [/SUP], Jerald Sadoff[SUP] 6 [/SUP], Glenda E Gray[SUP] 12 13 [/SUP], Beatriz Grinsztejn[SUP] 14 [/SUP], Paul A Goepfert[SUP] 15 [/SUP], Susan J Little[SUP] 16 [/SUP], Leonardo Paiva de Sousa[SUP] 14 [/SUP], Rebone Maboa[SUP] 17 [/SUP], April K Randhawa[SUP] 1 [/SUP], Michele P Andrasik[SUP] 1 [/SUP], Jenny Hendriks[SUP] 6 [/SUP], Carla Truyers[SUP] 5 [/SUP], Frank Struyf[SUP] 5 [/SUP], Hanneke Schuitemaker[SUP] 6 [/SUP], Macaya Douoguih[SUP] 6 [/SUP], James G Kublin[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 18 [/SUP], Kathleen M Neuzil[SUP] 19 [/SUP], Lindsay N Carpp[SUP] 1 [/SUP], Dean Follmann[SUP] 20 [/SUP], Peter B Gilbert[SUP] #[/SUP][SUP] 21 22 23 [/SUP], Richard A Koup[SUP] #[/SUP][SUP] 3 [/SUP], Ruben O Donis[SUP] #[/SUP][SUP] 7 [/SUP], Immune Assays Team; the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; and the United States Government (USG)/CoVPN Biostatistics Team
Affiliations
Abstract
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 (ID[SUB]50[/SUB]) 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 ID[SUB]50[/SUB]; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID[SUB]50[/SUB] (<2.7 IU[SUB]50[/SUB] ml[SUP]-1[/SUP]) and increased to 89% (78%, 96%) at ID[SUB]50[/SUB] = 96.3 IU[SUB]50[/SUB] ml[SUP]-1[/SUP]. Comparison of the vaccine efficacy by ID[SUB]50[/SUB] titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID[SUB]50[/SUB] titre as a correlate of protection across trials and vaccine types.
. 2022 Nov 10.
doi: 10.1038/s41564-022-01262-1. Online ahead of print.
Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial
Youyi Fong[SUP] 1 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP], David Benkeser[SUP] 4 [/SUP], Sanne Roels[SUP] 5 [/SUP], Daniel J Stieh[SUP] 6 [/SUP], An Vandebosch[SUP] 5 [/SUP], Mathieu Le Gars[SUP] 6 [/SUP], Griet A Van Roey[SUP] 6 [/SUP], Christopher R Houchens[SUP] 7 [/SUP], Karen Martins[SUP] 7 [/SUP], Lakshmi Jayashankar[SUP] 7 [/SUP], Flora Castellino[SUP] 7 [/SUP], Obrimpong Amoa-Awua[SUP] 3 [/SUP], Manjula Basappa[SUP] 3 [/SUP], Britta Flach[SUP] 3 [/SUP], Bob C Lin[SUP] 3 [/SUP], Christopher Moore[SUP] 3 [/SUP], Mursal Naisan[SUP] 3 [/SUP], Muhammed Naqvi[SUP] 3 [/SUP], Sandeep Narpala[SUP] 3 [/SUP], Sarah O'Connell[SUP] 3 [/SUP], Allen Mueller[SUP] 3 [/SUP], Leo Serebryannyy[SUP] 3 [/SUP], Mike Castro[SUP] 3 [/SUP], Jennifer Wang[SUP] 3 [/SUP], Christos J Petropoulos[SUP] 8 [/SUP], Alex Luedtke[SUP] 9 [/SUP], Ollivier Hyrien[SUP] 1 2 [/SUP], Yiwen Lu[SUP] 1 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Bhavesh Borate[SUP] 1 [/SUP], Lars W P van der Laan[SUP] 1 9 [/SUP], Nima S Hejazi[SUP] 1 10 [/SUP], Avi Kenny[SUP] 11 [/SUP], Marco Carone[SUP] 11 [/SUP], Daniel N Wolfe[SUP] 7 [/SUP], Jerald Sadoff[SUP] 6 [/SUP], Glenda E Gray[SUP] 12 13 [/SUP], Beatriz Grinsztejn[SUP] 14 [/SUP], Paul A Goepfert[SUP] 15 [/SUP], Susan J Little[SUP] 16 [/SUP], Leonardo Paiva de Sousa[SUP] 14 [/SUP], Rebone Maboa[SUP] 17 [/SUP], April K Randhawa[SUP] 1 [/SUP], Michele P Andrasik[SUP] 1 [/SUP], Jenny Hendriks[SUP] 6 [/SUP], Carla Truyers[SUP] 5 [/SUP], Frank Struyf[SUP] 5 [/SUP], Hanneke Schuitemaker[SUP] 6 [/SUP], Macaya Douoguih[SUP] 6 [/SUP], James G Kublin[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 18 [/SUP], Kathleen M Neuzil[SUP] 19 [/SUP], Lindsay N Carpp[SUP] 1 [/SUP], Dean Follmann[SUP] 20 [/SUP], Peter B Gilbert[SUP] #[/SUP][SUP] 21 22 23 [/SUP], Richard A Koup[SUP] #[/SUP][SUP] 3 [/SUP], Ruben O Donis[SUP] #[/SUP][SUP] 7 [/SUP], Immune Assays Team; the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; and the United States Government (USG)/CoVPN Biostatistics Team
Affiliations
- PMID: 36357712
- DOI: 10.1038/s41564-022-01262-1
Abstract
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 (ID[SUB]50[/SUB]) 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 ID[SUB]50[/SUB]; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID[SUB]50[/SUB] (<2.7 IU[SUB]50[/SUB] ml[SUP]-1[/SUP]) and increased to 89% (78%, 96%) at ID[SUB]50[/SUB] = 96.3 IU[SUB]50[/SUB] ml[SUP]-1[/SUP]. Comparison of the vaccine efficacy by ID[SUB]50[/SUB] titre curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine and the COV002-UK trial of the AZD1222 vaccine supported the ID[SUB]50[/SUB] titre as a correlate of protection across trials and vaccine types.