Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses
Creators: name: Einhauser, Sebastian
name: Asam, Claudia
name: Weps, Manuela
name: Senninger, Antonia
name: Peterhoff, David
name: Bauernfeind, Stilla
name: Asbach, Benedikt
name: Carnell, George William
name: Heeney, Jonathan Luke
name: Wytopil, Monika
name: Fuchs, André
name: Messmann, Helmut
name: Prelog, Martina
name: Liese, Johannes
name: Jeske, Samuel D.
name: Protzer, Ulrike
name: Hoelscher, Michael
name: Geldmacher, Christof
name: Überla, Klaus
name: Steininger, Philipp
name: Wagner, Ralf
name: Messmann, Helmut
name: Fuchs, Andre
name: Ebigbo, Alanna
name: Römmele, Christoph
name: Ullrich, Maximilian
name: Freitag, Marie
name: Traidl-Hoffmann, Claudia
name: Goekkaya, Mehmet
name: Metz, Aline
name: Holetschek, Corinna
name: Neumann, Avidan
name: Hoffmann, Reinhard
name: Kling, Elisabeth
name: Pruteanu, Mihail
name: Wibmer, Thomas
name: Rost, Susanne
name: Überla, Klaus
name: Steininger, Philipp
name: Wytopil, Monika
name: Beileke, Stephanie
name: Müller-Schmucker, Sandra
name: Korn, Klaus
name: Hastreiter, Tamara
name: Fraedrich, Kirsten
name: Obergfäll, Debora
name: Neumann, Frank
name: Kuhn, Claudia
name: Günther, Katja
name: Friedrich, Elke
name: Hoelscher, Michael
name: Wieser, Andreas
name: Geldmacher, Christof
name: Janke, Christian
name: Plank, Michael
name: Guggenbühl, Jessica
name: Reinkemeyer, Christina
name: Noreña, Ivan
name: Castelletti, Noemi
name: Acero, Raquel Rubio
name: Ahmed, M. I. M.
name: Diepers, Paulina
name: Eser, Tabea M.
name: Fuchs, Anna
name: Baranov, Olga
name: Bauer, Bernadette
name: Wang, Danni
name: Paunovic, Ivana
name: Protzer, Ulrike
name: Jeske, Samuel D.
name: Christa, Catharina
name: Tinnefeld, Kathrin
name: Vu, Martin
name: Willmann, Annika
name: Roggendorf, Hedwig
name: Körber, Nina
name: Bauer, Tanja
name: Gleich, Sabine
name: Wagner, Ralf
name: Asam, Claudia
name: Einhauser, Sebastian
name: Weps, Manuela
name: Senninger, Antonia
name: Carnell, George
name: Heeney, Jonathan Luke
name: Ebner, Antonia
name: José de Schultz, Maria
name: Rajes, Cedric
name: Al Wafai, Aya
name: Brenner, David
name: Sicheneder, Laura
name: Berr, Melanie
name: Schütz, Anja
name: Bauernfeind, Stilla
name: Hiergeist, Andreas
name: Gessner, André
name: Schmidt, Barbara
name: Niller, Hans-Helmut
name: Wenzel, Jürgen
name: Biermeier, Daniela
name: Lampl, Benedikt
name: Rothe, Ulrich
name: Gleißner, Ute
name: Brückner, Susanne
name: Treml, Michaela
name: Schedl, Holger
name: Biermaier, Beate
name: Achatz, Markus
name: Hierhammer, Daniela
name: Englhardt, Johanna
name: Scheidl, Werner
name: Jeyaraman, Sivaji
name: Schutt, Barbara
name: Liese, Johannes
name: Prelog, Martina
name: Almanzar, Giovanni
name: Schwägerl, Valeria
name: Bley, Julia
name: Vogt, Tim
name: Kousha, Kimia
name: Ziegler, Lars
name: Stein, Astrid
name: Förg, Franziska
name: Löw, Johann
name: Finkenberg, Barbara
name: Pollak, Dennis
name: Zamzow, Alexander
name: Eberbach, Nicole
name: Balkie, Lara
name: Kretzschmann, Tanja
name: Gehrig, Matthias
name: Bandorf, Matthias
name: Keck, Kilian
name: Allmanritter, Jan
name: Rafique, Shahid
name: Finster, Mona
name: Baumgart, Ingo
name: Heumüller-Klug, Sabine
name: Koglin, Hans-Jürgen
name: Gefeller, Olaf
name: Gall, Christine
name: Pfahlberg, Annette B.
name: Kaiser, Isabelle
name: Scheidt, Jörg
name: Drescher, Johannes
name: Siebenhaar, Yannic
name: Wogenstein, Florian
name: Reinel, Dirk
name: Weber, Beatrix
name: Zarzitzky, Fabian
name: Liebl, Bernhard
name: Herr, Caroline
name: Katz, Katharina
name: Sing, Andreas
name: Dangel, Alexandra
Publisher: name: Universität Regensburg
Year: 2024
Subjects: subject: SARS-CoV-2, COVID-19 breakthrough infection, Neutralization, Immune imprinting, Magnitude-breadth, Antigenic map, Machine learning
subject: 610 Medizin

description: 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, 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.