Randomized Controlled Trial

. 2023 Aug 22;77(4):560-564.

doi: 10.1093/cid/ciad209.

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial

Angela R Branche¹, Nadine G Rouphael², Cecilia Losada², Lindsey R Baden³, Evan J Anderson⁴, Anne F Luetkemeyer⁵, David J Diemert⁶, Patricia L Winokur⁷, Rachel M Presti⁸, Angelica C Kottkamp⁹, Ann R Falsey¹, Sharon E Frey¹⁰, Richard Rupp¹¹, Martín Bäcker¹², Richard M Novak¹³, Emmanuel B Walter¹⁴, Lisa A Jackson¹⁵, Susan J Little¹⁶, Lilly C Immergluck¹⁷, Siham M Mahgoub¹⁸, Jennifer A Whitaker¹⁹, Tara M Babu²⁰, Paul A Goepfert²¹, Dahlene N Fusco²², Robert L Atmar¹⁹, Christine M Posavad²³, Antonia Netzl²⁴, Derek J Smith²⁴, Kalyani Telu²⁵, Jinjian Mu²⁵, Mat Makowski²⁵, Mamodikoe K Makhene²⁶, Sonja Crandon²⁶, David C Montefiori²⁷, Paul C Roberts²⁶, John H Beigel²⁶

Affiliations

¹ Department of Medicine, University of Rochester VTEU, Rochester, New York, USA.
² Department of Medicine, Emory University Hope Clinic, Decatur, Georgia, USA.
³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Center for Childhood Infections and Vaccines (CCIV) of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, Georgia, USA.
⁵ Zuckerberg San Francisco General, University of California San Francisco, San Francisco, California, USA.
⁶ George Washington Vaccine Research Unit, George Washington University, Washington DC, USA.
⁷ Department of Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA.
⁸ Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
⁹ Department of Medicine, New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) Manhattan Research Clinic at NYU Grossman School of Medicine, New York, New York, USA.
¹⁰ Saint Louis University, Center for Vaccine Development, St. Louis, Missouri, USA.
¹¹ Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
¹² Department of Medicine, NYU VTEU Long Island Research Clinic at NYU Long Island School of Medicine, Mineola, New York, USA.
¹³ Department of Medicine, University of Illinois at Chicago-Project WISH, Chicago, Illinois, USA.
¹⁴ Department of Pediatrics, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁵ Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
¹⁶ Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.
¹⁷ Department of Microbiology/Biochemistry/Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA.
¹⁸ Department of Medicine, Howard University College of Medicine, Howard University Hospital, Washington DC, USA.
¹⁹ Departments of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Departments of Medicine, Epidemiology, and Laboratory Medicine & Pathology, University of Washington, Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
²¹ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²² Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
²³ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
²⁴ Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
²⁵ The Emmes Company, LLC, Rockville, Maryland, USA.
²⁶ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²⁷ Department of Surgery, Duke University, Durham, North Carolina, USA.

PMID: 37036397
PMCID: PMC10443997
DOI: 10.1093/cid/ciad209

Randomized Controlled Trial

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial

Angela R Branche et al. Clin Infect Dis. 2023.

. 2023 Aug 22;77(4):560-564.

doi: 10.1093/cid/ciad209.

Authors

Affiliations

¹ Department of Medicine, University of Rochester VTEU, Rochester, New York, USA.
² Department of Medicine, Emory University Hope Clinic, Decatur, Georgia, USA.
³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Center for Childhood Infections and Vaccines (CCIV) of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, Georgia, USA.
⁵ Zuckerberg San Francisco General, University of California San Francisco, San Francisco, California, USA.
⁶ George Washington Vaccine Research Unit, George Washington University, Washington DC, USA.
⁷ Department of Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA.
⁸ Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
⁹ Department of Medicine, New York University (NYU) Vaccine and Treatment Evaluation Unit (VTEU) Manhattan Research Clinic at NYU Grossman School of Medicine, New York, New York, USA.
¹⁰ Saint Louis University, Center for Vaccine Development, St. Louis, Missouri, USA.
¹¹ Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA.
¹² Department of Medicine, NYU VTEU Long Island Research Clinic at NYU Long Island School of Medicine, Mineola, New York, USA.
¹³ Department of Medicine, University of Illinois at Chicago-Project WISH, Chicago, Illinois, USA.
¹⁴ Department of Pediatrics, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁵ Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
¹⁶ Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.
¹⁷ Department of Microbiology/Biochemistry/Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA.
¹⁸ Department of Medicine, Howard University College of Medicine, Howard University Hospital, Washington DC, USA.
¹⁹ Departments of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Departments of Medicine, Epidemiology, and Laboratory Medicine & Pathology, University of Washington, Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
²¹ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²² Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
²³ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
²⁴ Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
²⁵ The Emmes Company, LLC, Rockville, Maryland, USA.
²⁶ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²⁷ Department of Surgery, Duke University, Durham, North Carolina, USA.

PMID: 37036397
PMCID: PMC10443997
DOI: 10.1093/cid/ciad209

Abstract

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Keywords: SARS-CoV-2; vaccine; variant.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. E. J. A. has received grants from Pfizer, Moderna, Janssen, GSK, Sanofi, Micron, and Regeneron through institution as well as consulting fees from Pfizer, Janssen, Moderna, and Sanofi. E. J. A. serves on safety/advisory boards for Sanofi, ACI Clinical/WCG and Kentucky Bioscience, Inc. A. R. B. has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, and Merck as well as consulting fees from Janssen and GSK. L. R. B. has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for Food and Drug Administration (FDA). L. R. B. is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. D. J. D. has received a contract from Leidos Biomedical research to conduct the clinical trial through institution. A. R. F. has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, and CyanVac through institution, consultant fees from Arrowhead and Icosavax, and honoraria as a speaker from Moderna and GlaxoSmithKline. A. R. F. also serves on safety/advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline. S. E. F. has received funding from Leidos to Saint Louis University to conduct Protocol DMID22-0004. D. N. F. has as a contract from Centers for Disease Control and Prevention (CDC) and is the site principal investigator (PI) for clinical trials from Gilead, Regeneron, and MetroBiotech, LLC. She is the PI on 1 investigator-initiated award from Gilead and the co-PI on another investigator-initiated award from Gilead. D. N. F. served on an HBV Advisory board for Gilead in 2021 and received payment for expert testimony not related to COVID in 2022. P. A. G. has received funding for COVAIL clinical trial. P. A. G. has also received consulting fees from Janssen Vaccines. L. C. I. has received support for the present manuscript from NIH-NIAID/DMID, Moderna, Pfizer, and Sanofi. L. C. I. has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, AHRQ, and NIH/NLM/NIMHD as well as consulting fees from Moderna, CDC, and Pediatric Emergency Medicine Associates, LLC. L. C. I. has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, and American Academy of Pediatrics- Georgia Chapter. L. C. I. serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and COVID-19 Task Force, Georgia. L. C. I. has a leadership role in the Pediatric Infectious Disease Society, serves as board member on the Emory University- Pediatric and Reproductive Environmental Health Scholars-Southeastern, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). L. C. I. has received travel/meeting support from the American Academy of Pediatrics and Moderna. L. A. J. has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. L. A. J. also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials. S. J. L. has received NIH grants through institution. A. F. L. has received grants from Merck, Gilead, and ViiV through institution as well as consulting fees from Vir Biotechnology. A. F. L. has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, and medication donated by Mayne Pharma to support research study. M. M. has received funding from Division of Microbiology and Infectious Diseases for contract number 75N93021C00012. D. C. M. has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines. J. M. has received funding from Division of Microbiology and Infectious Diseases, contract number 75N93021C00012. A. N. has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01. R. M. N. has received grants from Moderna and Janssen and travel/meeting support from Moderna. C. M. P. has received funding from NIAID UM1AI148684. R. M. P. has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna, and NIH through institution. N. G. R. has received research grants from Pfizer, Merck, Sanofi, Quidel, and Lilly through institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi. N. G. R. serves on safety committees for ICON and EMMES and is a member of the Moderna Advisory board. D. J. S. has received support from NIH-NIAID CEIRR, grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings. K. T. has received funding from Division of Microbiology and Infectious Diseases contract number 75N93021C00012. E. B. W. has received funding from Leidos Biomedical Research agreement number. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. E. B. W. has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. E. B. W. serves as member of Vaxcyte Scientific Advisory board. P. L. W. has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. P. L. W. has also received consulting fees from Pfizer and serves on safety/advisory board for Emmes Corporation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

**Figure 1.**
Pseudovirus neutralization ID₅₀ titers by timepoint (baseline, day 15, and day 29) and variant before and after vaccination with 30 mcg of Pfizer/BioNTech BNT162b2 Wildtype/Omicron BA.1 (A and C) or 30 mcg Pfizer/BioNTech BNT162b2 Wildtype/Omicron BA.4/BA.5 (B and D). Panels A and B show results from the Monogram lab for each vaccine candidate against D614G, Omicron BA.1 [B.1.1.529], BA.4/BA.5, B1.351 [Beta], B.1.617.2 [Delta] at baseline, days 15 and 29 post vaccination. Panels C and D show results from the Duke University Montefiori lab for each vaccine candidate against D614G, Omicron BA.1 [B.1.1.529], BA.4/BA.5, BQ.1.1, and XBB.1 at baseline and day 15 post-vaccination. Boxes with horizontal bars denote interquartile range (IQR) and median ID₅₀, respectively. Whisker denotes 95% confidence interval. Abbreviations: GMFR, geometric mean fold rise from baseline; GMT, geometric mean titer; ID₅₀, 50% neutralization; LLOD, lower limit of detection of the assay.

See this image and copyright information in PMC

Update of

Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial.
Branche AR, Rouphael NG, Losada C, Baden LR, Anderson EJ, Luetkemeyer AF, Diemert DJ, Winokur PL, Presti RM, Kottkamp AC, Falsey AR, Frey SE, Rupp R, Bäcker M, Novak RM, Walter EB, Jackson LA, Little SJ, Immergluck LC, Mahgoub SM, Whitaker JA, Babu TM, Goepfert PA, Fusco DN, Atmar RL, Posavad CM, Netzl A, Smith DJ, Telu K, Mu J, Makowski M, Makhene MK, Sonja C, Montefiori DC, Roberts PC, Beigel JH. Branche AR, et al. medRxiv [Preprint]. 2023 Mar 31:2023.01.31.23285306. doi: 10.1101/2023.01.31.23285306. medRxiv. 2023. Update in: Clin Infect Dis. 2023 Aug 22;77(4):560-564. doi: 10.1093/cid/ciad209. PMID: 37034641 Free PMC article. Updated. Preprint.

References

1. European Medicines Agency. EMA/117973/2021 - Reflection paper on the regulatory requirements for vaccines intended to provide protection against variant strain(s) of SARS-CoV-2. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-p.... Accessed February 2023.
1. U.S. Food and Drug Administration, COVID-19 Vaccines webpage. Available at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-dise.... Accessed February 2023.
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Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial

Affiliations

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Update of

References

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

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