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Long-term effects of homologous and heterologous SARS-CoV-2 vaccination on humoral and cellular immune responses
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  • Moritz M. Hollstein,
  • Lennart Münsterkötter,
  • Michael Schön,
  • Armin Bergmann,
  • Thea M. Husar,
  • Anna Abratis,
  • Abass Eidizadeh,
  • Sascha Dierks,
  • Meike Schaffrinski,
  • Karolin Zachmann,
  • Anne Schmitz,
  • Jason S. Holsapple,
  • Hedwig Stanisz-Bogeski,
  • Julie Schanz,
  • Andreas Fischer,
  • Uwe Groß,
  • Andreas Leha,
  • Andreas E. Zautner,
  • Moritz Schnelle,
  • Luise Erpenbeck
Moritz M. Hollstein
Universitatsmedizin Gottingen
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Lennart Münsterkötter
Universitatsmedizin Gottingen
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Michael Schön
Universitatsmedizin Gottingen
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Armin Bergmann
Universitatsmedizin Gottingen
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Thea M. Husar
Universitatsmedizin Gottingen
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Anna Abratis
Universitatsmedizin Gottingen
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Abass Eidizadeh
Universitatsmedizin Gottingen
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Sascha Dierks
Universitatsmedizin Gottingen
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Meike Schaffrinski
Universitatsmedizin Gottingen
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Karolin Zachmann
Universitatsmedizin Gottingen
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Anne Schmitz
Universitatsklinikum Munster
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Jason S. Holsapple
Universitatsklinikum Munster
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Hedwig Stanisz-Bogeski
Universitatsmedizin Gottingen
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Julie Schanz
Universitatsmedizin Gottingen
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Andreas Fischer
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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Moritz Schnelle
Universitatsmedizin Gottingen
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Luise Erpenbeck
Universitatsmedizin Gottingen
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Abstract

Background: Humoral and cellular immune responses to SARS-CoV-2 vaccines wane with time. In the COV‑ADAPT cohort, we recently studied both immunological components and their interdependencies following different vaccine combinations before (T1) and up to three months after second immunization (T2). This follow-up investigated the stability of long-term immune responses and aimed to identify predictive markers. Methods: We assessed humoral (anti-spike-RBD-IgG, neutralization capacity, avidity) and cellular (spike-induced T-cell interferon‑γ release) immune responses three-seven months after secondary vaccination (T3) in blood samples of 318 healthcare workers with previous homologous ChAdOx1 nCoV-19 (ChAdOx1), homologous BNT162b2 or heterologous ChAdOx1/BNT162b2 vaccinations. Results: At T3, homologous ChAdOx1 vaccination resulted in significantly lower anti-spike-RBD-IgG (152±151 BAU/ml) as compared to heterologous ChAdOx1/BNT162b2 (388±300 BAU/ml) and homologous BNT162b2 (435±327 BAU/ml). In all groups, anti-spike-RBD-IgG (T3) exceeded antibody levels before second vaccination (T1). T-cell interferon-γ release following heterologous ChAdOx1/BNT162b2 vaccination was significantly higher at T3 (1062±2083 mIU/ml) vs. T1 (680±1691 mIU/ml), yet did not differ significantly between the three groups at T3. Associations between humoral and cellular responses were found at T3 (all groups combined). Additionally, the early cellular response (at T1) was significantly associated with late (T3) humoral (ChAdOx1/BNT162b2, BNT162b2/BNT162b2) and cellular responses (all groups). In contrast to T2, neutralization capacity at T3 was significantly higher for ChAdOx1/BNT162b2 and BNT162b2/BNT162b2 vs. ChAdOx1/ChAdOx1. Conclusions: We identified (i) long-term interdependencies between the humoral and the cellular immune system, (ii) observed distinct waning dynamics following different vaccination regimes, and (iii) uncovered early T-cell responses as a useful predictor of long-term immune responses.