Original COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters

Luca M. Zaeck, Ngoc H. Tan, Wim J. R. Rietdijk, Daryl Geers, Roos S. G. Sablerolles, Susanne Bogers, Laura L. A. Dijk, Lennert Gommers, Leanne P. M. Leeuwen, Sharona Rugebregt, Abraham Goorhuis, Douwe F. Postma, Leo G. Visser, Virgil A. S. H. Dalm, Melvin Lafeber, Neeltje A. Kootstra, Anke L. W. Huckriede, Bart L. Haagmans, Debbie Baarle, Marion P. G. Koopmans, P. Hugo M. Kuy, Corine H. GeurtsvanKessel () and Rory D. Vries
Additional contact information
Luca M. Zaeck: Erasmus University Medical Center
Ngoc H. Tan: Erasmus University Medical Center
Wim J. R. Rietdijk: Erasmus University Medical Center
Daryl Geers: Erasmus University Medical Center
Roos S. G. Sablerolles: Erasmus University Medical Center
Susanne Bogers: Erasmus University Medical Center
Laura L. A. Dijk: Erasmus University Medical Center
Lennert Gommers: Erasmus University Medical Center
Leanne P. M. Leeuwen: Erasmus University Medical Center
Sharona Rugebregt: Erasmus University Medical Center
Abraham Goorhuis: Amsterdam University Medical Centers
Douwe F. Postma: University Medical Center Groningen
Leo G. Visser: Leiden University Medical Center
Virgil A. S. H. Dalm: Division of Allergy and Clinical Immunology, Erasmus University Medical Center
Melvin Lafeber: Erasmus University Medical Center
Neeltje A. Kootstra: Amsterdam Institute for Immunology and Infectious Diseases, University of Amsterdam
Anke L. W. Huckriede: University Medical Center Groningen, University of Groningen
Bart L. Haagmans: Erasmus University Medical Center
Debbie Baarle: University Medical Center Groningen, University of Groningen
Marion P. G. Koopmans: Erasmus University Medical Center
P. Hugo M. Kuy: Erasmus University Medical Center
Corine H. GeurtsvanKessel: Erasmus University Medical Center
Rory D. Vries: Erasmus University Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

Date: 2024
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DOI: 10.1038/s41467-024-48414-x

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