Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial

In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.

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Journal
iScience
Published
2025-10-01
DOI
https://doi.org/10.1016/j.isci.2025.113660
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial

Adrian B. McDermott, Avi Kenny, Rubén O. Donis, Michele P. Andrasik et al.
iScience
SARS-CoV-2 and COVID-19 Research
article

Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial

Adrian B. McDermott, Avi Kenny, Rubén O. Donis, Michele P. Andrasik, Nigel Garrett, Fei Heng, Leo Serebryannyy, Glenda Gray, Flora Castellino, Hanneke Schuitemaker, Johan Vingerhoets, Bob C. Lin, Obrimpong Amoa-Awua, Richard A. Koup, Jenny Hendriks, Alex Luedtke, Ying Huang, Beatriz Gilda Jegerhorn Grinsztejn, Allen Mueller, Manjula Basappa, Paul A. Goepfert, James G. Kublin, Susan J. Little, Craig A. Magaret, Britta Flach, Jerald Sadoff, April K. Randhawa, Patrice Delafontaine, Pavitra Roychoudhury, Lakshmi Jayashankar, Linda‐Gail Bekker, Edith Swann, Lars van der Laan, Christos J. Petropoulos, Macaya Douoguih, Aditya H. Gaur, Kathleen M. Neuzil, Yiwen Lu, Frank Struyf, Mike Castro, Dean A. Follmann, Sandeep Narpala, Ilse Van Dromme, Lawrence Corey, Alexander L. Greninger, Chenchen Yu, Martín Casapía, Youyi Fong, Sarah O’Connell, Daniel J Stieh, Griet A. Van Roey, Muhammed Naqvi, Marcelo Losso, Carla Truyers, Sanne Roels, Sandra Wagner Cardoso, Peter B. Gilbert, Lindsay Nicole Carpp, Marco Carone, Ollivier Hyrien, Mursal Naisan, Jennifer Wang, Christopher A. Moore, Victor Ayala, Mathieu Le Gars, Gabrielle Dziubla
article en

Abstract

In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.

iScienceVol. 28(11)
South African Medical Research Council (ZA), Tulane University (US), University of North Florida (US), University of Maryland, Baltimore (US), National Institutes of Health (US), St. Jude Children's Research Hospital (US), Johnson & Johnson (United States) (US), Desmond Tutu HIV Foundation (ZA), University of Cape Town (ZA), Duke University (US), University of the Witwatersrand (ZA), University of Washington (US), Centre for the AIDS Programme of Research in South Africa (ZA), Biomedical Advanced Research and Development Authority (US), LabCorp (United States) (US), Groote Schuur Hospital (ZA), Universidad Nacional de la Amazonía Peruana (PE), University of Alabama at Birmingham (US), University of California San Diego (US), Fred Hutch Cancer Center (US), Hospital Ramos Mejía (AR), Duke Institute for Health Innovation (US), National Institute of Allergy and Infectious Diseases (US), Perinatal HIV Research Unit (ZA), Janssen (Netherlands) (NL), Johnson & Johnson (Brazil) (BR), Fundação Oswaldo Cruz (BR), University of KwaZulu-Natal (ZA)
U.S. Department of Health and Human Services, Fred Hutchinson Cancer Research Center, National Institutes of Health, Biomedical Advanced Research and Development Authority, National Institute of Allergy and Infectious Diseases, Janssen Research and Development, Office of Research Infrastructure Programs, National Institutes of Health
Openalex Percentile: Top 60%
SARS-CoV-2 and COVID-19 Research
DOIOpen Access PDFOpenAlex
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