Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‐CoV‐2 vaccination

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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, and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses in blood samples up to 2 weeks before (T1) and 2–12 weeks following secondary immunization (T2).

Results

Initial vaccination with ChAdOx1 nCoV‐19 resulted in lower anti‐spike‐RBD‐IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p  < .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  < .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  < .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.

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  1. SciScore for 10.1101/2021.12.13.21267729: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The COV-ADAPT study was approved by the ethics committee of the University Medical Center Göttingen (21/5/21).
    Consent: After written informed consent was obtained, a questionnaire was handed out and blood samples were collected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.


    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.