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Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‑CoV‑2 vaccination
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  • Moritz M. Hollstein,
  • Lennart Münsterkötter,
  • Michael Schön,
  • Armin Bergmann,
  • Thea M. Husar,
  • Anna Abratis,
  • Abass Eidizadeh,
  • Meike Schaffrinski,
  • Karolin Zachmann,
  • Anne Schmitz,
  • Jason S. Holsapple,
  • Hedwig Stanisz-Bogeski,
  • Julie Schanz,
  • 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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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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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: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon‑γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. 
23 Dec 2021Submitted to Allergy
24 Dec 2021Submission Checks Completed
24 Dec 2021Assigned to Editor
25 Dec 2021Reviewer(s) Assigned
10 Jan 2022Review(s) Completed, Editorial Evaluation Pending
11 Jan 2022Editorial Decision: Revise Minor
18 Jan 20221st Revision Received
18 Jan 2022Submission Checks Completed
18 Jan 2022Assigned to Editor
18 Jan 2022Reviewer(s) Assigned
19 Jan 2022Review(s) Completed, Editorial Evaluation Pending
23 Jan 2022Editorial Decision: Accept
16 Feb 2022Published in Allergy. 10.1111/all.15247