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.

Details

Title
Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine
Author
Benkeser, David 1 ; Fong, Youyi 2 ; Janes, Holly E. 2 ; Kelly, Elizabeth J. 3 ; Hirsch, Ian 4 ; Sproule, Stephanie 5 ; Stanley, Ann Marie 3   VIAFID ORCID Logo  ; Maaske, Jill 6 ; Villafana, Tonya 6 ; Houchens, Christopher R. 7 ; Martins, Karen 7 ; Jayashankar, Lakshmi 7 ; Castellino, Flora 7 ; Ayala, Victor 7 ; Petropoulos, Christos J. 8 ; Leith, Andrew 9 ; Haugaard, Deanne 9 ; Webb, Bill 9 ; Lu, Yiwen 10 ; Yu, Chenchen 10 ; Borate, Bhavesh 10 ; van der Laan, Lars W. P. 11 ; Hejazi, Nima S. 12   VIAFID ORCID Logo  ; Carpp, Lindsay N. 10   VIAFID ORCID Logo  ; Randhawa, April K. 10   VIAFID ORCID Logo  ; Andrasik, Michele P. 10 ; Kublin, James G. 10   VIAFID ORCID Logo  ; Isaacs, Margaret Brewinski 13 ; Makhene, Mamodikoe 14 ; Tong, Tina 15 ; Robb, Merlin L. 16   VIAFID ORCID Logo  ; Corey, Lawrence 17   VIAFID ORCID Logo  ; Neuzil, Kathleen M. 18 ; Follmann, Dean 19 ; Hoffman, Corey 7 ; Falsey, Ann R. 20 ; Sobieszczyk, Magdalena 21 ; Koup, Richard A. 22 ; Donis, Ruben O. 7   VIAFID ORCID Logo  ; Gilbert, Peter B. 23   VIAFID ORCID Logo 

1  Rollins School of Public Health, Emory University, Department of Biostatistics and Bioinformatics, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
2  Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); Fred Hutchinson Cancer Center, Public Health Sciences Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
3  BioPharmaceuticals R&D, AstraZeneca, Translational Medicine, Vaccines & Immune Therapies, Gaithersburg, USA (GRID:grid.418152.b) (ISNI:0000 0004 0543 9493) 
4  Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (GRID:grid.417815.e) (ISNI:0000 0004 5929 4381) 
5  Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA (GRID:grid.418152.b) (ISNI:0000 0004 0543 9493) 
6  Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA (GRID:grid.418152.b) (ISNI:0000 0004 0543 9493) 
7  Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services, Washington, USA (GRID:grid.476870.a) 
8  LabCorp-Monogram Biosciences, South San Francisco, USA (GRID:grid.419316.8) (ISNI:0000 0004 0550 1859) 
9  Nexelis, Seattle, USA (GRID:grid.419316.8) 
10  Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
11  Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Statistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
12  Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); T.H. Chan School of Public Health, Harvard University, Department of Biostatistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
13  Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.419681.3) (ISNI:0000 0001 2164 9667) 
14  Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA (GRID:grid.419681.3) (ISNI:0000 0001 2164 9667) 
15  Vaccine Translational Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, USA (GRID:grid.419681.3) (ISNI:0000 0001 2164 9667) 
16  Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166) 
17  Rollins School of Public Health, Emory University, Department of Biostatistics and Bioinformatics, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502); University of Washington, Department of Laboratory Medicine and Pathology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
18  University of Maryland School of Medicine, Center for Vaccine Development and Global Health, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
19  National Institutes of Health, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
20  University of Rochester, Division of Infectious Diseases, Department of Medicine, Rochester, USA (GRID:grid.16416.34) (ISNI:0000 0004 1936 9174) 
21  Columbia University Irving Medical Center and New York-Presbyterian Hospital, Division of Infectious Diseases, Department of Medicine, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
22  National Institutes of Health, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
23  Fred Hutchinson Cancer Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); Fred Hutchinson Cancer Center, Public Health Sciences Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); School of Public Health, University of Washington, Department of Biostatistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
Pages
36
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20590105
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41541-023-00630-0
ProQuest document ID
2785501607
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.