Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial

Bo Zhang; Youyi Fong; Jonathan Fintzi; Eric Chu; Holly E Janes; Avi Kenny; Marco Carone; David Benkeser; Lars W P van der Laan; Weiping Deng; Honghong Zhou; Xiaowei Wang; Yiwen Lu; Chenchen Yu; Bhavesh Borate; Haiyan Chen; Isabel Reeder; Lindsay N Carpp; Christopher R Houchens; Karen Martins; Lakshmi Jayashankar; Chuong Huynh; Carl J Fichtenbaum; Spyros Kalams; Cynthia L Gay; Michele P Andrasik; James G Kublin; Lawrence Corey; Kathleen M Neuzil; Frances Priddy; Rituparna Das; Bethany Girard; Hana M El Sahly; Lindsey R Baden; Thomas Jones; Ruben O Donis; Richard A Koup; Peter B Gilbert; Dean Follmann; United States Government (USG) COVID-19 Immune Assays Team; Moderna, Inc. Team; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team; USG/CoVPN Biostatistics Team

doi:10.1038/s41467-024-52348-9

Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial

Nat Commun. 2024 Sep 11;15(1):7954. doi: 10.1038/s41467-024-52348-9.

Authors

Bo Zhang¹, Youyi Fong^{1

2}, Jonathan Fintzi³, Eric Chu⁴, Holly E Janes^{1

2}, Avi Kenny⁵, Marco Carone⁵, David Benkeser⁶, Lars W P van der Laan⁷, Weiping Deng⁸, Honghong Zhou⁸, Xiaowei Wang⁸, Yiwen Lu¹, Chenchen Yu¹, Bhavesh Borate¹, Haiyan Chen⁹, Isabel Reeder⁹, Lindsay N Carpp¹, Christopher R Houchens⁹, Karen Martins⁹, Lakshmi Jayashankar⁹, Chuong Huynh⁹, Carl J Fichtenbaum¹⁰, Spyros Kalams¹¹, Cynthia L Gay¹², Michele P Andrasik¹, James G Kublin¹, Lawrence Corey^{1

13}, Kathleen M Neuzil^{14

15}, Frances Priddy⁸, Rituparna Das⁸, Bethany Girard⁸, Hana M El Sahly¹⁶, Lindsey R Baden¹⁷, Thomas Jones⁹, Ruben O Donis⁹, Richard A Koup¹⁸, Peter B Gilbert^{1

2

5}, Dean Follmann¹⁹; United States Government (USG) COVID-19 Immune Assays Team; Moderna, Inc. Team; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team; USG/CoVPN Biostatistics Team

Collaborator

Lars W P van der Laan

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
² Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁴ Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁵ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁷ Department of Statistics, University of Washington, Seattle, WA, USA.
⁸ Moderna, Inc, Cambridge, MA, USA.
⁹ Biomedical Advanced Research and Development Authority, Washington, DC, USA.
¹⁰ Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH, USA.
¹¹ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹² Department of Medicine, Division of Infectious Diseases, UNC HIV Cure Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
¹³ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹⁴ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁵ Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
¹⁶ Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
¹⁷ Brigham and Women's Hospital, Boston, MA, USA.
¹⁸ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁹ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. dfollmann@niaid.nih.gov.

Abstract

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase III

MeSH terms

2019-nCoV Vaccine mRNA-1273* / administration & dosage
2019-nCoV Vaccine mRNA-1273* / immunology
Adult
Antibodies, Neutralizing* / immunology
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
COVID-19 Vaccines / administration & dosage
COVID-19 Vaccines / immunology
COVID-19* / immunology
COVID-19* / prevention & control
COVID-19* / virology
Female
Humans
Immunization, Secondary*
Male
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus* / immunology
Vaccine Efficacy

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
2019-nCoV Vaccine mRNA-1273
COVID-19 Vaccines
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding