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

Author

Listed:
  • Bo Zhang

    (Fred Hutchinson Cancer Center)

  • Youyi Fong

    (Fred Hutchinson Cancer Center
    Fred Hutchinson Cancer Center)

  • Jonathan Fintzi

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Eric Chu

    (Frederick National Laboratory for Cancer Research)

  • Holly E. Janes

    (Fred Hutchinson Cancer Center
    Fred Hutchinson Cancer Center)

  • Avi Kenny

    (University of Washington)

  • Marco Carone

    (University of Washington)

  • David Benkeser

    (Emory University)

  • Lars W. P. Laan

    (University of Washington)

  • Weiping Deng

    (Moderna, Inc)

  • Honghong Zhou

    (Moderna, Inc)

  • Xiaowei Wang

    (Moderna, Inc)

  • Yiwen Lu

    (Fred Hutchinson Cancer Center)

  • Chenchen Yu

    (Fred Hutchinson Cancer Center)

  • Bhavesh Borate

    (Fred Hutchinson Cancer Center)

  • Haiyan Chen

    (Biomedical Advanced Research and Development Authority)

  • Isabel Reeder

    (Biomedical Advanced Research and Development Authority)

  • Lindsay N. Carpp

    (Fred Hutchinson Cancer Center)

  • Christopher R. Houchens

    (Biomedical Advanced Research and Development Authority)

  • Karen Martins

    (Biomedical Advanced Research and Development Authority)

  • Lakshmi Jayashankar

    (Biomedical Advanced Research and Development Authority)

  • Chuong Huynh

    (Biomedical Advanced Research and Development Authority)

  • Carl J. Fichtenbaum

    (University of Cincinnati)

  • Spyros Kalams

    (Vanderbilt University Medical Center)

  • Cynthia L. Gay

    (University of North Carolina at Chapel Hill School of Medicine)

  • Michele P. Andrasik

    (Fred Hutchinson Cancer Center)

  • James G. Kublin

    (Fred Hutchinson Cancer Center)

  • Lawrence Corey

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Kathleen M. Neuzil

    (University of Maryland School of Medicine
    Fogarty International Center, National Institutes of Health)

  • Frances Priddy

    (Moderna, Inc)

  • Rituparna Das

    (Moderna, Inc)

  • Bethany Girard

    (Moderna, Inc)

  • Hana M. El Sahly

    (Baylor College of Medicine)

  • Lindsey R. Baden

    (Brigham and Women’s Hospital)

  • Thomas Jones

    (Biomedical Advanced Research and Development Authority)

  • Ruben O. Donis

    (Biomedical Advanced Research and Development Authority)

  • Richard A. Koup

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Peter B. Gilbert

    (Fred Hutchinson Cancer Center
    Fred Hutchinson Cancer Center
    University of Washington)

  • Dean Follmann

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

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.

Suggested Citation

  • Bo Zhang & Youyi Fong & Jonathan Fintzi & Eric Chu & Holly E. Janes & Avi Kenny & Marco Carone & David Benkeser & Lars W. P. Laan & Weiping Deng & Honghong Zhou & Xiaowei Wang & Yiwen Lu & Chenchen Yu, 2024. "Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52348-9
    DOI: 10.1038/s41467-024-52348-9
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    References listed on IDEAS

    as
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