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. van Dijk, Lennert Gommers, Leanne P. M. van Leeuwen, Sharona Rugebregt, Abraham Goorhuis, Douwe F. Postma, Leo G. Visser, Virgil A. S. H. Dalm, Melvin Lafeber, Neeltje A. Kootstra, Anke Huckriede, Bart L. Haagmans, Debbie van Baarle, Marion Koopmans, Anna van de Hoef, Isabelle Veerman Roders, Nathalie Tjon, Karenin van Grafhorst, Nella J. Nieuwkoop, Faye de Wilt, Sandra Scherbeijn, Babs E. Verstrepen, Marion Ferren, Kim Handrejk, Katharina S. Schmitz, Koen Wijnans, Aldert C. P. Lamoré, Jenny L Schnyder, O S Starozhitskaya, Agnes M. Harskamp, Irma Maurer, Brigitte Boeser‐Nunnink, Marga Mangas-Ruiz, Renate Akkerman, Martin Beukema, Jacqueline J. de Vries-Idema, Sander Nijhof, Frederique Visscher, Jopie Zuidema, Jessica A. Vlot, Eva Spaargaren, Naomi Olthof, Annelies van Wengen‐Stevenhagen, Anouk J. E. de Vreede, Jytte Blokland, Simone van Mill, Vivian W. M. Slagter, Kitty Suijk-Benschop, Jos Fehrmann-Naumann, Daphne Bart, Elysia van der Hulst, P.H.M. van der Kuy, Corine H. GeurtsvanKessel, Rory D. de Vries
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.