Open Access

Sebastian Einhauser, Claudia Asam, Manuela Weps, Antonia Senninger, David Peterhoff, Stilla Bauernfeind, Benedikt Asbach, George William Carnell, Jonathan Luke Heeney, Monika Wytopil, André Fuchs, Helmut Messmann, Martina Prelog, Johannes Liese, Samuel D. Jeske, Ulrike Protzer, Michael Hoelscher, Christof Geldmacher, Klaus Überla, Philipp Steiniger, Ralf Wagner, Alanna Ebigbo, Christoph Römmele, Maximilian Ullrich, Marie Freitag, Claudia Traidl-Hoffmann, Mehmet Goekkaya, Aline Metz, Corinna Holetschek, Avidan Neumann, Reinhard Neumann, Elisabeth Kling, Mihail Pruteanu, Thomas Wibmer, Susanne Rost, Stephanie Beileke, Sandra Müller-Schmucker, Klaus Korn, Tamara Hastreiter, Kirsten Fraedrich, Debora Obergfäll, Frank Neumann, Claudia Kuhn, Katja Günther, Elke Friedrich, Andreas Wieser, Christian Janke, Michael Plank, Jessica Guggenbühl, Christina Reinkemeyer, Ivan Noreña, Noemi Castelletti, Raquel Rubio Acero, M. I. M. Ahmed, Paulina Diepers, Tabea M. Eser, Anna Fuchs, Olga Baranov, Bernadette Bauer, Danni Wang, Ivana Paunovic, Catharina Christa, Kathrin Tinnefeld, Martin Vu, Annika Willmann, Hedwig Roggendorf, Nina Körber, Tanja Bauer, Sabine Gleich, Antonia Ebner, Maria José de Schultz, Cedric Rajes, Aya Al Wafai, David Brenner, Laura Sicheneder, Melanie Berr, Anja Schütz, Andreas Hiergeist, André Gessner, Barbara Schmidt, Hans-Helmut Niller, Jürgen Wenzel, Daniela Biermeier, Benedikt Lampl, Ulrich Rothe, Ute Gleißner, Susanne Brückner, Michaela Treml, Holger Schedl, Beate Biermaier, Markus Achatz, Daniela Hierhammer, Johanna Englhardt, Werner Scheidl, Sivaji Jeyaraman, Barbara Schutt, Giovanni Almanzar, Valeria Schwägerl, Julia Bley, Tim Vogt, Kimia Kousha, Lars Ziegler, Astrid Stein, Franziska Förg, Johann Löw, Barbara Finkenberg, Dennis Pollak, Alexander Zamzow, Nicole Eberbach, Lara Balkie, Tanja Kretzschmann, Matthias Gehrig, Matthias Bandorf, Kilian Keck, Jan Allmanritter, Shahid Rafique, Mona Finster, Ingo Baumgart, Sabine Heumüller-Klug, Hans-Jürgen Koglin, Olaf Gefeller, Christine Gall, Annette B. Pfahlberg, Isabelle Kaiser, Jörg Scheidt, Johannes Drescher, Yannic Siebenhaar, Florian Wogenstein, Dirk Reinel, Beatrix Weber, Fabian Zarzitzky, Bernhard Liebl, Caroline Herr, Katharina Katz, Andreas Sing, Alexandra Dangel

• Background The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study. Methods 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1. Findings Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple-vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, aBackground The impact of the infecting SARS-CoV-2 variant of concern (VOC) and the vaccination status was determined on the magnitude, breadth, and durability of the neutralizing antibody (nAb) profile in a longitudinal multicentre cohort study. Methods 173 vaccinated and 56 non-vaccinated individuals were enrolled after SARS-CoV-2 Alpha, Delta, or Omicron infection and visited four times within 6 months and nAbs were measured for D614G, Alpha, Delta, BA.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and JN.1. Findings Magnitude-breadth-analysis showed enhanced neutralization capacity in vaccinated individuals against multiple VOCs. Longitudinal analysis revealed sustained neutralization magnitude-breadth after antigenically distant Delta or Omicron breakthrough infection (BTI), with triple-vaccinated individuals showing significantly elevated titres and improved breadth. Antigenic mapping and antibody landscaping revealed initial boosting of vaccine-induced WT-specific responses after BTI, a shift in neutralization towards infecting VOCs at peak responses and an immune imprinted bias towards dominating WT immunity in the long-term. Despite that bias, machine-learning models confirmed a sustained shift of the immune-profiles following BTI. Interpretation In summary, our longitudinal analysis revealed delayed and short lived nAb shifts towards the infecting VOC, but an immune imprinted bias towards long-term vaccine induced immunity after BTI. Funding This work was funded by the Bavarian State Ministry of Science and the Arts for the CoVaKo study and the ForCovid project. The funders had no influence on the study design, data analysis or data interpretation.…