Cited by 1,137SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studiesvaccines and immunoinformatics approaches

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial

Open access
Gilbert, Peter B., Montefiori, David C., McDermott, Adrian B., Fong, Youyi, Benkeser, David, Deng, Weiping, Zhou, Honghong, Houchens, Christopher R. +36 more·2022·Science

Published version of a preprint

Abstract

Antibody levels predict vaccine efficacy: Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK

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  • Neutralizing antibodies are one of the key parameters correlating with the observed protective efficacy of the first-generation SARS-CoV-2 mRNA vaccine CVnCoV and a licensed COVID-19 mRNA vaccine.

    “Neutralizing antibodies in the sera of the participants will be assessed since they have been identified as one of the key parameters correlating with the observed protective efficacy of the first generation SARS-CoV-2 mRNA vaccine CVnCoV27, and a licensed COVID-19 mRNA vaccine28.”

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Research works printed but not linked: 5

  1. [1]Centers for Disease Control and Prevention. COVID-19 Vaccines and Vaccination. CDC COVID-19 Science Briefs. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Atlanta (GA). [Updated 2021 May 27]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570435/. 2021. 34009769
  2. [13]Moderna. Moderna Announces TeenCOVE Study of its COVID-19 Vaccine in Adolescents Meets Primary Endpoint and Plans to Submit Data to Regulators in Early June. Press Release. 25 May, 2021. Access date 21 Jun, 2021. Available at https://investors.modernatx.com/news-releases/news-releasedetails/moderna-announces-teencove-study-its-covid-19-vaccine.
  3. [29]Regeneron. Phase 3 Prevention Trial Showed 81% Reduced Risk of Symptomatic SARS-CoV-2 Infections with Subcutaneous Administration of REGEN-COV™ (casirivimab with imdevimab). Press Release. 12 Apr, 2021. Access date 22 Jun, 2021. Available at https://investor.regeneron.com/newsreleases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars.
  4. [40]Benkeser D, Díaz I, Ran J. Inference for natural mediation effects under case-cohort sampling with applications in identifying COVID-19 vaccine correlates of protection [Preprint] Access date 13 Jul, 2021. arXiv:210302643 [statME] 2021.
  5. [41]Westfall PH, Young SS. Resampling-based multiple testing: Examples and methods for p-value adjustment: John Wiley & Sons; 1993.

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Authors
Gilbert, P. B., Montefiori, D. C., McDermott, A. B., Fong, Y., Benkeser, D., Deng, W., Zhou, H., Houchens, C. R., Martins, K., Jayashankar, L., Castellino, F., Flach, B., Lin, B. C., O’Connell, S., McDanal, C., Eaton, A., Sarzotti-Kelsoe, M., Lu, Y., Yu, C., Borate, B., van der Laan, L. W. P., Hejazi, N. S., Huynh, C., Miller, J., El Sahly, H. M., Baden, L. R., Baron, M., De La Cruz, L., Gay, C., Kalams, S., Kelley, C. F., Andrasik, M. P., Kublin, J. G., Corey, L., Neuzil, K. M., Carpp, L. N., Pajon, R., Follmann, D., Donis, R. O., Koup, R. A., Immune Assays Team§, Moderna, I. T., Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team§, & United States Government (USG)/CoVPN Biostatistics Team§
Affiliations
  • University of Washington (US)
  • Duke University (US)
  • National Institutes of Health (US)
  • Fred Hutch Cancer Center (US)
  • Emory University (US)
  • Moderna Therapeutics (United States) (US)
  • Biomedical Advanced Research and Development Authority (US)
  • Department of Surgery and Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
  • Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  • Brigham and Women's Hospital (US)
  • Palm Beach Research Center (US)
  • Keystone Vitalink Research, Greenville, SC, USA.
  • University of North Carolina at Chapel Hill (US)
  • Vanderbilt University Medical Center (US)
  • University of Maryland, Baltimore (US)
  • Moderna, Inc., Cambridge, MA, USA.
  • Biomedical Advanced Research and Development Authority, Washington, DC, USA.
Corresponding author
  • Gilbert, Peter B.
  • Montefiori, David C.
  • McDermott, Adrian B.
  • Koup, Richard A.
Venue
Science
Published
2022-01-07
Volume
375
Issue
6576
Pages
43-50
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W3217661335
Cited by
1,137
References
47
Citations by year
2026: 65 · 2025: 114 · 2024: 197 · 2023: 278 · 2022: 412 · 2021: 69
FWCI
123.36
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Wellcome Trust
  • National Institutes of Health (1s10od028685-01, UL1TR002384)
  • National Institute of Allergy and Infectious Diseases (S10AI174104, U01AI068635, UM1AI068614, UM1AI068635, UM1AI148575, UM1AI069476, R37AI054165, UM1AI148684, UM1AI069412)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
mRNA-1273 vaccine, COVID-19 vaccine efficacy, SARS-CoV-2, neutralizing antibodies, binding antibodies, correlates of protection, vaccine immunogenicity, vaccine approval

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