npj Vaccines (Mar 2023)
Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine
- David Benkeser,
- Youyi Fong,
- Holly E. Janes,
- Elizabeth J. Kelly,
- Ian Hirsch,
- Stephanie Sproule,
- Ann Marie Stanley,
- Jill Maaske,
- Tonya Villafana,
- Christopher R. Houchens,
- Karen Martins,
- Lakshmi Jayashankar,
- Flora Castellino,
- Victor Ayala,
- Christos J. Petropoulos,
- Andrew Leith,
- Deanne Haugaard,
- Bill Webb,
- Yiwen Lu,
- Chenchen Yu,
- Bhavesh Borate,
- Lars W. P. van der Laan,
- Nima S. Hejazi,
- Lindsay N. Carpp,
- April K. Randhawa,
- Michele P. Andrasik,
- James G. Kublin,
- Margaret Brewinski Isaacs,
- Mamodikoe Makhene,
- Tina Tong,
- Merlin L. Robb,
- Lawrence Corey,
- Kathleen M. Neuzil,
- Dean Follmann,
- Corey Hoffman,
- Ann R. Falsey,
- Magdalena Sobieszczyk,
- Richard A. Koup,
- Ruben O. Donis,
- Peter B. Gilbert,
- on behalf of the AstraZeneca AZD1222 Clinical Study Group,
- the Immune Assays Team,
- the United States Government (USG)/CoVPN Biostatistics Team
Affiliations
- David Benkeser
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University
- Youyi Fong
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Holly E. Janes
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Elizabeth J. Kelly
- Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Ian Hirsch
- Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Stephanie Sproule
- Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Ann Marie Stanley
- Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Jill Maaske
- Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Tonya Villafana
- Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
- Christopher R. Houchens
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Karen Martins
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Lakshmi Jayashankar
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Flora Castellino
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Victor Ayala
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Christos J. Petropoulos
- LabCorp-Monogram Biosciences
- Andrew Leith
- Nexelis
- Deanne Haugaard
- Nexelis
- Bill Webb
- Nexelis
- Yiwen Lu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Chenchen Yu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Bhavesh Borate
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lars W. P. van der Laan
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Nima S. Hejazi
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- April K. Randhawa
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Michele P. Andrasik
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- James G. Kublin
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Margaret Brewinski Isaacs
- Division of AIDS, National Institute of Allergy and Infectious Diseases
- Mamodikoe Makhene
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Tina Tong
- Vaccine Translational Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Merlin L. Robb
- US Military HIV Research Program, Walter Reed Army Institute of Research
- Lawrence Corey
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University
- Kathleen M. Neuzil
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine
- Dean Follmann
- Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Corey Hoffman
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Ann R. Falsey
- Division of Infectious Diseases, Department of Medicine, University of Rochester
- Magdalena Sobieszczyk
- Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center and New York-Presbyterian Hospital
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Ruben O. Donis
- Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services
- Peter B. Gilbert
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- on behalf of the AstraZeneca AZD1222 Clinical Study Group
- the Immune Assays Team
- the United States Government (USG)/CoVPN Biostatistics Team
- DOI
- https://doi.org/10.1038/s41541-023-00630-0
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 13
Abstract
Abstract In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was −5.8% (−651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.
