Nature Communications (Nov 2024)
Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial
- Lindsay N. Carpp,
- Ollivier Hyrien,
- Youyi Fong,
- David Benkeser,
- Sanne Roels,
- Daniel J. Stieh,
- Ilse Van Dromme,
- Griet A. Van Roey,
- Avi Kenny,
- Ying Huang,
- Marco Carone,
- Adrian B. McDermott,
- Christopher R. Houchens,
- Karen Martins,
- Lakshmi Jayashankar,
- Flora Castellino,
- Obrimpong Amoa-Awua,
- Manjula Basappa,
- Britta Flach,
- Bob C. Lin,
- Christopher Moore,
- Mursal Naisan,
- Muhammed Naqvi,
- Sandeep Narpala,
- Sarah O’Connell,
- Allen Mueller,
- Leo Serebryannyy,
- Mike Castro,
- Jennifer Wang,
- Christos J. Petropoulos,
- Alex Luedtke,
- Yiwen Lu,
- Chenchen Yu,
- Michal Juraska,
- Nima S. Hejazi,
- Daniel N. Wolfe,
- Jerald Sadoff,
- Glenda E. Gray,
- Beatriz Grinsztejn,
- Paul A. Goepfert,
- Linda-Gail Bekker,
- Aditya H. Gaur,
- Valdilea G. Veloso,
- April K. Randhawa,
- Michele P. Andrasik,
- Jenny Hendriks,
- Carla Truyers,
- An Vandebosch,
- Frank Struyf,
- Hanneke Schuitemaker,
- Macaya Douoguih,
- James G. Kublin,
- Lawrence Corey,
- Kathleen M. Neuzil,
- Dean Follmann,
- Richard A. Koup,
- Ruben O. Donis,
- Peter B. Gilbert,
- On behalf of the Immune Assays Team,
- the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team,
- the United States Government (USG)/CoVPN Biostatistics Team
Affiliations
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Ollivier Hyrien
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Youyi Fong
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- David Benkeser
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University
- Sanne Roels
- Johnson & Johnson Innovative Medicine
- Daniel J. Stieh
- Janssen Vaccines and Prevention
- Ilse Van Dromme
- Johnson & Johnson Innovative Medicine
- Griet A. Van Roey
- Janssen Vaccines and Prevention
- Avi Kenny
- Department of Biostatistics, University of Washington School of Public Health
- Ying Huang
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Marco Carone
- Department of Biostatistics, University of Washington School of Public Health
- Adrian B. McDermott
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- 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
- Flora Castellino
- Biomedical Advanced Research and Development Authority
- Obrimpong Amoa-Awua
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Manjula Basappa
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Britta Flach
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Bob C. Lin
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Christopher Moore
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Mursal Naisan
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Muhammed Naqvi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Sandeep Narpala
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Sarah O’Connell
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Allen Mueller
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Leo Serebryannyy
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Mike Castro
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Jennifer Wang
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Christos J. Petropoulos
- LabCorp-Monogram Biosciences
- Alex Luedtke
- Department of Statistics, University of Washington
- Yiwen Lu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Chenchen Yu
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Michal Juraska
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Nima S. Hejazi
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Daniel N. Wolfe
- Biomedical Advanced Research and Development Authority
- Jerald Sadoff
- Janssen Vaccines and Prevention
- Glenda E. Gray
- Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand
- Beatriz Grinsztejn
- Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz
- Paul A. Goepfert
- Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham
- Linda-Gail Bekker
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory
- Aditya H. Gaur
- Department of Infectious Diseases, St. Jude Children’s Research Hospital
- Valdilea G. Veloso
- Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz
- April K. Randhawa
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Michele P. Andrasik
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Jenny Hendriks
- Janssen Vaccines and Prevention
- Carla Truyers
- Johnson & Johnson Innovative Medicine
- An Vandebosch
- Johnson & Johnson Innovative Medicine
- Frank Struyf
- Johnson & Johnson Innovative Medicine
- Hanneke Schuitemaker
- Janssen Vaccines and Prevention
- Macaya Douoguih
- Janssen Vaccines and Prevention
- James G. Kublin
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- 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
- 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
- Peter B. Gilbert
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- On behalf of the Immune Assays Team
- the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team
- the United States Government (USG)/CoVPN Biostatistics Team
- DOI
- https://doi.org/10.1038/s41467-024-53727-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 18
Abstract
Abstract Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90th percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.
