Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany

  1. Alex Dulovic
  2. Barbora Kessel
  3. Manuela Harries
  4. Matthias Becker
  5. Julia Ortmann
  6. Johanna Griesbaum
  7. Jennifer Jüngling
  8. Daniel Junker
  9. Pilar Hernandez
  10. Daniela Gornyk
  11. Stephan Glöckner
  12. Vanessa Melhorn
  13. Stefanie Castell
  14. Jana-Kristin Heise
  15. Yvonne Kemmling
  16. Torsten Tonn
  17. Kerstin Frank
  18. Thomas Illig
  19. Norman Klopp
  20. Neha Warikoo
  21. Angelika Rath
  22. Christina Suckel
  23. Anne Ulrike Marzian
  24. Nicole Grupe
  25. Philipp D. Kaiser
  26. Bjoern Traenkle
  27. Ulrich Rothbauer
  28. Tobias Kerrinnes
  29. Gérard Krause
  30. Berit Lange
  31. Nicole Schneiderhan-Marra
  32. Monika Strengert

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Abstract

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.

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  1. Version published to 10.3389/fimmu.2022.828053
  2. ScreenIT

    SciScore for 10.1101/2021.12.01.21266960: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    To generate a heat map for comparing antigen-specific antibodies formation across different vaccination schemes within the mix and max sample cohort,
    antigen-specific
    suggested: None
    To evaluate longitudinal changes in antibody response and ACE2 binding inhibition within our longitudinal sample cohort, changes from T1 to T2 were calculated using log2 fold change.
    ACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    2.5 Data analysis and statistics: Initial results collation and matching to metadata was done in Excel 2016 and R 4.1.0 (32).
    Excel
    suggested: None
    Graphs were exported from RStudio and further edited in Inkscape (Version 0.92.4) to generate final figures.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    Inkscape
    suggested: (Inkscape, RRID:SCR_014479)

    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: We detected the following sentences addressing limitations in the study:
    Our manuscript has several limitations, namely that we are only measuring antibodies (including neutralizing antibodies) that are present within serum. As previously stated, we have used an ACE2-RBD competition assay to measure inhibition of ACE2 binding instead of classical virus neutralization assays, although the results of this assay have already been shown to be similar to VNT and are known to be specific to neutralizing antibody responses only. While neutralizing antibodies themselves are considered a strong correlate for protection (13), other components that are not measured within our assays such as T-cell mediated immunity will also offer protection (52, 53). Our use of serum also means that memory B-cells, which are involved in protection against severe disease progression (54), are equally excluded from our analysis. Our study cohort consists of relatively low sample numbers for both heterologous and Ad26.CoV2.S vaccinations whereas BNT162b2 samples are overrepresented. However, our sample numbers are similar or in the case of Ad26.CoV2.S exceed other previously published work making our study one of the largest independent evaluation studies of this vaccine. Our BNT162b2 sample size mimics dose distribution in Germany where approximately 70% of delivered vaccine doses were from Pfizer. Our study population is also relatively similar in regard to age and gender. Overall, we provide data on the vaccine-induced humoral response for all currently available mRNA-, vec...

    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.
    • No protocol registration statement was detected.

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

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  3. Version published to 10.1101/2021.12.01.21266960 on medRxiv