Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

  1. Matthias Becker
  2. Alex Dulovic
  3. Daniel Junker
  4. Natalia Ruetalo
  5. Philipp D. Kaiser
  6. Yudi T. Pinilla
  7. Constanze Heinzel
  8. Julia Haering
  9. Bjoern Traenkle
  10. Teresa R. Wagner
  11. Mirjam Layer
  12. Martin Mehrlaender
  13. Valbona Mirakaj
  14. Jana Held
  15. Hannes Planatscher
  16. Katja Schenke-Layland
  17. Gérard Krause
  18. Monika Strengert
  19. Tamam Bakchoul
  20. Karina Althaus
  21. Rolf Fendel
  22. Andrea Kreidenweiss
  23. Michael Koeppen
  24. Ulrich Rothbauer
  25. Michael Schindler
  26. Nicole Schneiderhan-Marra

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Abstract

SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.

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  1. Version published to 10.1038/s41467-021-23473-6
  2. ScreenIT

    SciScore for 10.1101/2021.03.08.21252958: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved the Ethics Committee of Eberhard Karls University and the University Hospital Tübingen under the approval number 312/2020BO1 (Coro-Buddy) to Dr. Andrea Kreidenweiss, Institute for Tropical Medicine, University Hospital Tübingen and Eberhard Karls University Tübingen, and 312/2020BO2 to Dr. Karina Althaus, Institute for Clinical and Experimental Transfusion Medicine, University Hospital Tübingen.
    Consent: All participants gave written informed consent.
    RandomizationThe experiments were not randomized and the investigators were not blinded during either experimentation or data analysis Study recruitment, sample collection and ethics statement: Serum and saliva samples were collected from healthcare workers, vaccinated with the Pfizer BNT-162b2 vaccine.
    BlindingThe experiments were not randomized and the investigators were not blinded during either experimentation or data analysis Study recruitment, sample collection and ethics statement: Serum and saliva samples were collected from healthcare workers, vaccinated with the Pfizer BNT-162b2 vaccine.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Saliva samples were analyzed for SARS-CoV-2 wild-type RBD reactive IgG antibodies by an in-house ELISA developed at the Institute of Tropical Medicine, University of Tübingen.
    SARS-CoV-2 wild-type RBD reactive IgG
    suggested: None
    Cells were incubated for 1 hour at RT with 100 µL of serum from a hospitalized convalescent donor in a 1:10,000 dilution and washed 3 times with PBS. 100 µL of goat anti-human Alexa594 (1:2,000) in PBS was used as a secondary antibody for 1 hour at RT.
    anti-human Alexa594
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, Caco-2 cells were cultured at 37°C with 5% CO2 in Dulbecco’s modified Eagle medium (DMEM), supplemented with 10% fetal calf serum (FCS), 2 mM L-glutamine, 100 mg/mL penicillin-streptomycin and 1% non-essential amino acids (NEAA).
    Caco-2
    suggested: None
    Software and Algorithms
    SentencesResources
    For quantification of infection rates, images were taken with the Cytation3 (BioTek) and DAPI-positive and Alexa 594-positive cells were automatically counted by the Gen5 software (BioTek)
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    Virus neutralizing titers (VNT50S) were calculated as the half-maximal inhibitory dose (ID50) using 4-parameter nonlinear regression (GraphPad Prism).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Figures were generated in Rstudio and then edited for clarity in Inkscape (Inkscape 0.92.4).
    Rstudio
    suggested: (RStudio, RRID:SCR_000432)
    Pre-processing of data such as matching sample metadata and collecting results from multiple assay runs was performed in Excel 2016.
    Excel
    suggested: None
    GraphPad Prism version 8.4.0 was used to process VNT data.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.03.08.21252958v1 on medRxiv