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; AstraZeneca AZD1222 Clinical Study Group; Immune Assays Team; United States Government (USG)/CoVPN Biostatistics Team

doi:10.1038/s41541-023-00630-0

Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine

NPJ Vaccines. 2023 Mar 11;8(1):36. doi: 10.1038/s41541-023-00630-0.

Authors

David Benkeser¹, Youyi Fong^{2

3}, Holly E Janes^{2

3}, Elizabeth J Kelly⁴, Ian Hirsch⁵, Stephanie Sproule⁶, Ann Marie Stanley⁴, Jill Maaske⁷, Tonya Villafana⁷, Christopher R Houchens⁸, Karen Martins⁸, Lakshmi Jayashankar⁸, Flora Castellino⁸, Victor Ayala⁸, Christos J Petropoulos⁹, Andrew Leith¹⁰, Deanne Haugaard¹⁰, Bill Webb¹⁰, Yiwen Lu², Chenchen Yu², Bhavesh Borate², Lars W P van der Laan^{2

11}, Nima S Hejazi^{2

12}, Lindsay N Carpp², April K Randhawa², Michele P Andrasik², James G Kublin², Margaret Brewinski Isaacs¹³, Mamodikoe Makhene¹⁴, Tina Tong¹⁵, Merlin L Robb¹⁶, Lawrence Corey^{1

17}, Kathleen M Neuzil¹⁸, Dean Follmann¹⁹, Corey Hoffman⁸, Ann R Falsey²⁰, Magdalena Sobieszczyk²¹, Richard A Koup^#²², Ruben O Donis^#⁸, Peter B Gilbert^#^{23

24

25}; AstraZeneca AZD1222 Clinical Study Group; Immune Assays Team; United States Government (USG)/CoVPN Biostatistics Team

Affiliations

¹ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁴ Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁵ Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
⁶ Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁷ Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁸ Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services, Washington, DC, USA.
⁹ LabCorp-Monogram Biosciences, South San Francisco, CA, USA.
¹⁰ Nexelis, Seattle, WA, USA.
¹¹ Department of Statistics, University of Washington, Seattle, WA, USA.
¹² Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³ Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
¹⁴ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁵ Vaccine Translational Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
¹⁶ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹⁷ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹⁸ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁹ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁰ Division of Infectious Diseases, Department of Medicine, University of Rochester, Rochester, NY, USA.
²¹ Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center and New York-Presbyterian Hospital, New York, NY, USA.
²² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²³ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. pgilbert@fredhutch.org.
²⁴ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. pgilbert@fredhutch.org.
²⁵ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA. pgilbert@fredhutch.org.

^# Contributed equally.

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.

Abstract

Grants and funding