Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost
Abstract Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic’s evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate’s contemporary performance. For 985 recipients of an mRNA...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41467-025-55931-w |
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| author | Bo Zhang Youyi Fong Lauren Dang Jonathan Fintzi Shiyu Chen Jing Wang Nadine G. Rouphael Angela R. Branche David J. Diemert Ann R. Falsey Daniel S. Graciaa Lindsey R. Baden Sharon E. Frey Jennifer A. Whitaker Susan J. Little Satoshi Kamidani Emmanuel B. Walter Richard M. Novak Richard Rupp Lisa A. Jackson Chenchen Yu Craig A. Magaret Cindy Molitor Bhavesh Borate Sydney Busch David Benkeser Antonia Netzl Derek J. Smith Tara M. Babu Angelica C. Kottkamp Anne F. Luetkemeyer Lilly C. Immergluck Rachel M. Presti Martín Bäcker Patricia L. Winokur Siham M. Mahgoub Paul A. Goepfert Dahlene N. Fusco Robert L. Atmar Christine M. Posavad Jinjian Mu Mat Makowski Mamodikoe K. Makhene Seema U. Nayak Paul C. Roberts Peter B. Gilbert Dean Follmann Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team |
| author_facet | Bo Zhang Youyi Fong Lauren Dang Jonathan Fintzi Shiyu Chen Jing Wang Nadine G. Rouphael Angela R. Branche David J. Diemert Ann R. Falsey Daniel S. Graciaa Lindsey R. Baden Sharon E. Frey Jennifer A. Whitaker Susan J. Little Satoshi Kamidani Emmanuel B. Walter Richard M. Novak Richard Rupp Lisa A. Jackson Chenchen Yu Craig A. Magaret Cindy Molitor Bhavesh Borate Sydney Busch David Benkeser Antonia Netzl Derek J. Smith Tara M. Babu Angelica C. Kottkamp Anne F. Luetkemeyer Lilly C. Immergluck Rachel M. Presti Martín Bäcker Patricia L. Winokur Siham M. Mahgoub Paul A. Goepfert Dahlene N. Fusco Robert L. Atmar Christine M. Posavad Jinjian Mu Mat Makowski Mamodikoe K. Makhene Seema U. Nayak Paul C. Roberts Peter B. Gilbert Dean Follmann Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team |
| author_sort | Bo Zhang |
| collection | DOAJ |
| description | Abstract Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic’s evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate’s contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 (“COVID-19”) and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal (“predicted-at-exposure”) titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate. |
| format | Article |
| id | doaj-art-9eb1f5b0e20d472d95848bd2b7992217 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-9eb1f5b0e20d472d95848bd2b79922172025-01-19T12:31:40ZengNature PortfolioNature Communications2041-17232025-01-0116111910.1038/s41467-025-55931-wNeutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boostBo Zhang0Youyi Fong1Lauren Dang2Jonathan Fintzi3Shiyu Chen4Jing Wang5Nadine G. Rouphael6Angela R. Branche7David J. Diemert8Ann R. Falsey9Daniel S. Graciaa10Lindsey R. Baden11Sharon E. Frey12Jennifer A. Whitaker13Susan J. Little14Satoshi Kamidani15Emmanuel B. Walter16Richard M. Novak17Richard Rupp18Lisa A. Jackson19Chenchen Yu20Craig A. Magaret21Cindy Molitor22Bhavesh Borate23Sydney Busch24David Benkeser25Antonia Netzl26Derek J. Smith27Tara M. Babu28Angelica C. Kottkamp29Anne F. Luetkemeyer30Lilly C. Immergluck31Rachel M. Presti32Martín Bäcker33Patricia L. Winokur34Siham M. Mahgoub35Paul A. Goepfert36Dahlene N. Fusco37Robert L. Atmar38Christine M. Posavad39Jinjian Mu40Mat Makowski41Mamodikoe K. Makhene42Seema U. Nayak43Paul C. Roberts44Peter B. Gilbert45Dean Follmann46Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study TeamVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterClinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer ResearchHope Clinic, Emory UniversityVaccine and Treatment Evaluation Unit, University of RochesterGeorge Washington Vaccine Research Unit, George Washington UniversityVaccine and Treatment Evaluation Unit, University of RochesterHope Clinic, Emory UniversityDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Vaccine Development, Saint Louis UniversityDepartment of Molecular Virology and Microbiology and Department of Medicine, Baylor College of MedicineDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San DiegoCenter for Childhood Infections and Vaccines, Children’s Healthcare of AtlantaDuke Human Vaccine Institute, Duke University School of MedicineProject WISH, University of Illinois at ChicagoDepartment of Pediatrics, University of Texas Medical BranchKaiser Permanente Washington Health Research InstituteVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory UniversityDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory UniversityCenter for Pathogen Evolution, Department of Zoology, University of CambridgeCenter for Pathogen Evolution, Department of Zoology, University of CambridgeDivision of Allergy and Infectious Diseases, Department of Medicine, University of WashingtonVaccine and Treatment Evaluation Unit, Manhattan Research Clinic, New York University Grossman School of MedicineDivision of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, University of CaliforniaClinical Research Center, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Internal Medicine, University of Utah Schoole of MedicineDepartment of Medicine, University of Iowa College of MedicineHoward University College of Medicine, Howard University HospitalDepartment of Medicine, University of Alabama at BirminghamDepartment of Medicine, Tulane University School of MedicineDepartment of Molecular Virology and Microbiology and Department of Medicine, Baylor College of MedicineInfectious Diseases Clinical Research Consortium (IDCRC) Laboratory Operations Unit, Fred Hutchinson Cancer CenterThe Emmes Company LLCThe Emmes Company LLCDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic’s evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate’s contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 (“COVID-19”) and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal (“predicted-at-exposure”) titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.https://doi.org/10.1038/s41467-025-55931-w |
| spellingShingle | Bo Zhang Youyi Fong Lauren Dang Jonathan Fintzi Shiyu Chen Jing Wang Nadine G. Rouphael Angela R. Branche David J. Diemert Ann R. Falsey Daniel S. Graciaa Lindsey R. Baden Sharon E. Frey Jennifer A. Whitaker Susan J. Little Satoshi Kamidani Emmanuel B. Walter Richard M. Novak Richard Rupp Lisa A. Jackson Chenchen Yu Craig A. Magaret Cindy Molitor Bhavesh Borate Sydney Busch David Benkeser Antonia Netzl Derek J. Smith Tara M. Babu Angelica C. Kottkamp Anne F. Luetkemeyer Lilly C. Immergluck Rachel M. Presti Martín Bäcker Patricia L. Winokur Siham M. Mahgoub Paul A. Goepfert Dahlene N. Fusco Robert L. Atmar Christine M. Posavad Jinjian Mu Mat Makowski Mamodikoe K. Makhene Seema U. Nayak Paul C. Roberts Peter B. Gilbert Dean Follmann Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost Nature Communications |
| title | Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost |
| title_full | Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost |
| title_fullStr | Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost |
| title_full_unstemmed | Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost |
| title_short | Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost |
| title_sort | neutralizing antibody immune correlates in covail trial recipients of an mrna second covid 19 vaccine boost |
| url | https://doi.org/10.1038/s41467-025-55931-w |
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