Immune correlates analysis of the ENSEMBLE single Ad26.COV2.S dose vaccine efficacy clinical trial

被引：53

作者：

Fong, Youyi ^{[1
,2
]}

McDermott, Adrian B. ^{[3
]}

Benkeser, David ^{[4
]}

Roels, Sanne ^{[5
]}

Stieh, Daniel J. ^{[6
]}

Vandebosch, An ^{[5
]}

Le Gars, Mathieu ^{[6
]}

Van Roey, Griet A. ^{[6
]}

Houchens, Christopher R. ^{[7
]}

Martins, Karen ^{[7
]}

Jayashankar, Lakshmi ^{[7
]}

Castellino, Flora ^{[7
]}

Amoa-Awua, Obrimpong ^{[3
]}

Basappa, Manjula ^{[3
]}

Flach, Britta ^{[3
]}

Lin, Bob C. ^{[3
]}

Moore, Christopher ^{[3
]}

Naisan, Mursal ^{[3
]}

Naqvi, Muhammed ^{[3
]}

Narpala, Sandeep ^{[3
]}

O'Connell, Sarah ^{[3
]}

Mueller, Allen ^{[3
]}

Serebryannyy, Leo ^{[3
]}

Castro, Mike ^{[3
]}

Wang, Jennifer ^{[3
]}

Petropoulos, Christos J. ^{[8
]}

Luedtke, Alex ^{[9
]}

Hyrien, Ollivier ^{[1
,2
]}

Lu, Yiwen ^{[1
]}

Yu, Chenchen ^{[1
]}

Borate, Bhavesh ^{[1
]}

van der Laan, Lars W. P. ^{[1
,9
]}

Hejazi, Nima S. ^{[1
,10
]}

Kenny, Avi ^{[11
]}

Carone, Marco ^{[11
]}

Wolfe, Daniel N. ^{[7
]}

Sadoff, Jerald ^{[6
]}

Gray, Glenda E. ^{[12
,13
]}

Grinsztejn, Beatriz ^{[14
]}

Goepfert, Paul A. ^{[15
]}

Little, Susan J. ^{[16
]}

de Sousa, Leonardo Paiva ^{[14
]}

Maboa, Rebone ^{[17
]}

Randhawa, April K. ^{[1
]}

Andrasik, Michele P. ^{[1
]}

Hendriks, Jenny ^{[6
]}

Truyers, Carla ^{[5
]}

Struyf, Frank ^{[5
]}

Schuitemaker, Hanneke ^{[6
]}

Douoguih, Macaya ^{[6
]}

机构：

[1] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[2] Fred Hutchinson Canc Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[3] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

[5] Janssen R&D, Beerse, Belgium

[6] Janssen Vaccines & Prevent, Leiden, Netherlands

[7] Biomed Adv Res & Dev Author, Washington, DC USA

[8] LabCorp Monogram Biosci, San Francisco, CA USA

[9] Univ Washington, Dept Stat, Seattle, WA 98195 USA

[10] Weill Cornell Med, Dept Populat Hlth Sci, Div Biostat, Sch Publ Hlth, New York, NY USA

[11] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA

[12] Univ Witwatersrand, Fac Hlth Sci, Perinatal HIV Res Unit, Johannesburg, South Africa

[13] South African Med Res Council, Cape Town, South Africa

[14] Fundacao Oswaldo Cruz, Evandro Chagas Natl Inst Infect Dis, Rio De Janeiro, Brazil

[15] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA

[16] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA

[17] Ndlovu Elandsdoorn Site, Limpopo, Dennilton, South Africa

[18] Univ Washington, Dept Lab Med & Pathol, Seattle, WA USA

[19] Univ Maryland, Sch Med, Ctr Vaccine Dev & Global Hlth, Baltimore, MD 21201 USA

[20] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

NATURE MICROBIOLOGY | 2022年 / 7卷 / 12期

基金：

美国国家卫生研究院;

关键词：

PROTECTION;

D O I：

10.1038/s41564-022-01262-1

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：1996 / +

页数：32

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