Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial

Angela R. Branche, Department of Medicine, Division of Infectious Diseases, University of Rochester, Rochester, NY, USA. angela_branche@urmc.rochester.edu.
Nadine G. Rouphael, Hope Clinic, Emory University, Decatur, GA, USA.
David J. Diemert, George Washington Vaccine Research Unit, George Washington University, Washington D.C., WA, USA.
Ann R. Falsey, Department of Medicine, Division of Infectious Diseases, University of Rochester, Rochester, NY, USA.
Cecilia Losada, Hope Clinic, Emory University, Decatur, GA, USA.
Lindsey R. Baden, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sharon E. Frey, Center for Vaccine Development, Saint Louis University, St. Louis, MO, USA.
Jennifer A. Whitaker, Departments of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, TX, USA.
Susan J. Little, Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Evan J. Anderson, Center for Childhood Infections and Vaccines (CCIV) of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA, USA.
Emmanuel B. Walter, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Richard M. Novak, Project WISH, University of Illinois at Chicago, Chicago, IL, USA.
Richard Rupp, University of Texas Medical Branch, Galveston, TX, USA.
Lisa A. Jackson, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Tara M. Babu, Departments of Medicine, Epidemiology and Laboratory Medicine and Pathology, University of Washington, Vaccines and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Angelica C. Kottkamp, NYU VTEU Manhattan Research Clinic, NYU Grossman School of Medicine, New York, NY, USA.
Anne F. Luetkemeyer, Zuckerberg San Francisco General, University of California San Francisco, San Francisco, CA, USA.
Lilly C. Immergluck, Department of Microbiology, Biochemistry and Immunology, and Clinical Research Center, Morehouse School of Medicine, Atlanta, GA, USA.
Rachel M. Presti, Washington University School of Medicine, St. Louis, MO, USA.
Martín Bäcker, NYU VTEU Long Island Research Clinic, NYU Long Island School of Medicine, Mineola, NY, USA.
Patricia L. Winokur, College of Medicine, University of Iowa, Iowa City, IA, USA.
Siham M. Mahgoub, Howard University College of Medicine, Howard University Hospital, Washington D.C., WA, USA.
Paul A. Goepfert, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Dahlene N. Fusco, Tulane University School of Medicine, New Orleans, LA, USA.
Elissa Malkin, George Washington Vaccine Research Unit, George Washington University, Washington D.C., WA, USA.
Jeffrey M. Bethony, George Washington Vaccine Research Unit, George Washington University, Washington D.C., WA, USA.
Edward E. Walsh, Department of Medicine, Division of Infectious Diseases, University of Rochester, Rochester, NY, USA.
Daniel S. Graciaa, Hope Clinic, Emory University, Decatur, GA, USA.
Hady Samaha, Hope Clinic, Emory University, Decatur, GA, USA.
Amy C. Sherman, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Stephen R. Walsh, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Getahun Abate, Center for Vaccine Development, Saint Louis University, St. Louis, MO, USA.

Document Type

Journal Article

Publication Date

8-28-2023

Journal

Nature medicine

DOI

10.1038/s41591-023-02503-4

Abstract

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

Department

Medicine

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