Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses

Abstract

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.

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Titel	Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses
Medien	eBioMedicine
Band	110
Verfasser	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 Steininger, Ralf Wagner, Christine Gall, Andreas Wieser, Sandra M. Müller-Schmucker, Stephanie Beileke, Mehmet Goekkaya, Elisabeth Kling, Raquel Rubio-Acero, Michael Plank, Catharina Christa, Annika Willmann, Martin Vu, Benedikt M.J. Lampl, Giovanni Almanzar, Kimia Kousha, Valeria Schwägerl, Bernhard Liebl, Prof. Dr. Beatrix Weber, Johannes Drescher, Prof. Dr. Jörg Scheidt, Yannic Siebenhaar, Dirk Reinel, Florian Wogenstein, Olaf Gefeller, Group Covako-Study
Seiten	105438
Veröffentlichungsdatum	08.11.2024
Zitation	Einhauser, Sebastian; Asam, Claudia; Weps, Manuela; Senninger, Antonia; Peterhoff, David; Bauernfeind, Stilla; Asbach, Benedikt; Carnell, George William; Heeney, Jonathan Luke; Wytopil, Monika; Fuchs, André; Messmann, Helmut; Prelog, Martina; Liese, Johannes; Jeske, Samuel D.; Protzer, Ulrike; Hoelscher, Michael; Geldmacher, Christof; Überla, Klaus; Steininger, Philipp; Wagner, Ralf; Gall, Christine; Wieser, Andreas; Müller-Schmucker, Sandra M.; Beileke, Stephanie; Goekkaya, Mehmet; Kling, Elisabeth; Rubio-Acero, Raquel; Plank, Michael; Christa, Catharina; Willmann, Annika; Vu, Martin; Lampl, Benedikt M.J.; Almanzar, Giovanni; Kousha, Kimia; Schwägerl, Valeria; Liebl, Bernhard; Weber, Beatrix; Drescher, Johannes; Scheidt, Jörg; Siebenhaar, Yannic; Reinel, Dirk; Wogenstein, Florian; Gefeller, Olaf; Covako-Study, Group (2024): Longitudinal effects of SARS-CoV-2 breakthrough infection on imprinting of neutralizing antibody responses. eBioMedicine 110, 105438. DOI: 10.1016/j.ebiom.2024.105438