Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.
Journal: Nature communications
Volume: 15
Issue: 1
Year of Publication: 2024
Affiliated Institutions:
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Johnson & Johnson Innovative Medicine, Beerse, Belgium.
Janssen Vaccines and Prevention, Leiden, the Netherlands.
Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Biomedical Advanced Research and Development Authority, Washington, DC, USA.
LabCorp-Monogram Biosciences, South San Francisco, CA, USA.
Department of Statistics, University of Washington, Seattle, WA, USA.
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Evandro Chagas National Institute of Infectious Diseases-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. pgilbert@fredhutch.org.
Abstract summary
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 90 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.
Authors & Co-authors:
Carpp Lindsay N LN
Hyrien Ollivier O
Fong Youyi Y
Benkeser David D
Roels Sanne S
Stieh Daniel J DJ
Van Dromme Ilse I
Van Roey Griet A GA
Kenny Avi A
Huang Ying Y
Carone Marco M
McDermott Adrian B AB
Houchens Christopher R CR
Martins Karen K
Jayashankar Lakshmi L
Castellino Flora F
Amoa-Awua Obrimpong O
Basappa Manjula M
Flach Britta B
Lin Bob C BC
Moore Christopher C
Naisan Mursal M
Naqvi Muhammed M
Narpala Sandeep S
O'Connell Sarah S
Mueller Allen A
Serebryannyy Leo L
Castro Mike M
Wang Jennifer J
Petropoulos Christos J CJ
Luedtke Alex A
Lu Yiwen Y
Yu Chenchen C
Juraska Michal M
Hejazi Nima S NS
Wolfe Daniel N DN
Sadoff Jerald J
Gray Glenda E GE
Grinsztejn Beatriz B
Goepfert Paul A PA
Bekker Linda-Gail LG
Gaur Aditya H AH
Veloso Valdilea G VG
Randhawa April K AK
Andrasik Michele P MP
Hendriks Jenny J
Truyers Carla C
Vandebosch An A
Struyf Frank F
Schuitemaker Hanneke H
Douoguih Macaya M
Kublin James G JG
Corey Lawrence L
Neuzil Kathleen M KM
Follmann Dean D
Koup Richard A RA
Donis Ruben O RO
Gilbert Peter B PB
Study Outcome
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