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Humoral and cellular immune responses in fully vaccinated individuals with or without SARS-CoV-2 breakthrough infection: results from the CoV‑ADAPT cohort
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  • Moritz Schnelle,
  • Moritz M. Hollstein,
  • Sascha Dierks,
  • Michael P. Schön,
  • Armin Bergmann,
  • Anna Abratis,
  • Abass Eidizadeh,
  • Sarah Kaltenbach,
  • Julie Schanz,
  • Uwe Groß,
  • Andreas Leha,
  • Andreas E. Zautner,
  • Andreas Fischer,
  • Luise Erpenbeck
Moritz Schnelle
Universitatsmedizin Gottingen

Corresponding Author:[email protected]

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Moritz M. Hollstein
Universitatsmedizin Gottingen
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Sascha Dierks
Universitatsmedizin Gottingen
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Michael P. Schön
Universitatsmedizin Gottingen
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Armin Bergmann
Universitatsmedizin Gottingen
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Anna Abratis
Universitatsmedizin Gottingen
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Abass Eidizadeh
Universitatsmedizin Gottingen
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Sarah Kaltenbach
Universitatsmedizin Gottingen
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Julie Schanz
Universitatsmedizin Gottingen
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Uwe Groß
Universitatsmedizin Gottingen
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Andreas Leha
Universitatsmedizin Gottingen
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Andreas E. Zautner
Universitatsmedizin Gottingen
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Andreas Fischer
Universitatsmedizin Gottingen
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Luise Erpenbeck
Universitatsmedizin Gottingen
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Abstract

Despite recent advances in prophylactic vaccination, SARS-CoV-2 infections continue to cause significant morbidity. A better understanding of immune response differences between vaccinated individuals with and without later SARS-CoV-2 breakthrough infection is urgently needed. CoV-ADAPT is a prospective long-term study comparing humoral (anti-spike-RBD-IgG, neutralization capacity, avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in individuals vaccinated against SARS-CoV-2 at four different time points (three before and one after third vaccination). In this cohort study, 62 fully vaccinated individuals presented with SARS‑CoV-2 breakthrough infections vs 151 without infection 3-7 months following third vaccination. Breakthrough infections significantly increased anti-spike-RBD-IgG (p<0.01), but not spike-directed T-cell interferon-γ release (TC), antibody neutralization capacity or avidity. Anti-spike-RBD-IgG and antibody avidity decreased with age (p<0.01) and females showed higher anti-spike-RBD-IgG (p<0.01), and a tendency towards higher antibody avidity (p=0.051). The association between humoral and cellular immune responses previously reported at various time points was lost in subjects after breakthrough infections (p=0.807). Finally, a machine-learning approach based on our large immunological data set (a total of 49 variables) from different time points was unable to predict breakthrough infections (AUC: 0.55). In conclusion, distinct differences in humoral vs cellular immune responses in fully vaccinated individuals with or without breakthrough infection could be demonstrated. Breakthrough infections predominantly drive the humoral response without boosting the cellular component. Breakthrough infections could not be predicted based on immunological data, which indicates a superior role of environmental factors (e.g. virus exposure) in individualized risk assessment.
31 Mar 2023Submitted to Journal of Medical Virology
03 Apr 2023Submission Checks Completed
03 Apr 2023Assigned to Editor
03 Apr 2023Review(s) Completed, Editorial Evaluation Pending
18 Apr 2023Reviewer(s) Assigned
29 Jun 2023Editorial Decision: Revise Major
16 Aug 20231st Revision Received
25 Aug 2023Submission Checks Completed
25 Aug 2023Assigned to Editor
25 Aug 2023Review(s) Completed, Editorial Evaluation Pending
25 Aug 2023Reviewer(s) Assigned
13 Sep 2023Editorial Decision: Accept