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Einhauser, S.* ; Asam, C.* ; Weps, M.* ; Senninger, A.* ; Peterhoff, D.* ; Bauernfeind, S.* ; Asbach, B.* ; Carnell, G.W.* ; Heeney, J.L.* ; Wytopil, M.* ; Fuchs, A.* ; Messmann, H.* ; Prelog, M.* ; Liese, J.* ; Jeske, S.D.* ; Protzer, U. ; Hoelscher, M.* ; Geldmacher, C.* ; Überla, K.* ; Steininger, P.* ; Wagner, R.*

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

EBioMedicine 110:105438 (2024)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Antigenic Map ; Covid-19 Breakthrough Infection ; Immune Imprinting ; Machine Learning ; Magnitude-breadth ; Neutralization ; Sars-cov-2

ISSN (print) / ISBN 2352-3964

e-ISSN 2352-3964

Journal EBioMedicine

Quellenangaben Volume: 110, Article Number: 105438

Publisher Elsevier

Publishing Place Amsterdam [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)