SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against SARS-CoV-2 Delta and Omicron that can be predicted by anti-S antibody concentrations in serological assays

  1. Alina Seidel
  2. Bernd Jahrsdörfer
  3. Sixten Körper
  4. Dan Albers
  5. Pascal von Maltitz
  6. Rebecca Müller
  7. Ramin Lotfi
  8. Patrick Wuchter
  9. Harald Klüter
  10. Michael Schmidt
  11. Jan Münch
  12. Hubert Schrezenmeier

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Abstract

Background

Recent data on immune evasion of new SARS-CoV-2 variants raise concerns about antibody-based COVID-19 therapies. Therefore in this study the in-vitro neutralization capacity against SARS-CoV-2 variants Wuhan D614G, Delta and Omicron in sera of convalescent individuals with and without boost by vaccination was assessed.

Methods and Findings

This in-vitro study included 66 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=29) and with SARS-CoV-2 vaccination (n=37). We measured SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against Wuhan D614G, Delta and Omicron in a pseudovirus neutralization assay.

Sera of the majority of unvaccinated convalescents did not effectively neutralize Delta and Omicron (4/29, 13.8% and 19/29, 65.5%, resp.). Neutralizing titers against Wuhan D614G, Delta and Omicron were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 11.1, 15.3 and 60-fold higher geometric mean of 50%-neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after vaccination. Concentrations of anti-S antibodies in the serological assays anti-SARS-CoV-2 QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S predict neutralization capacity against Wuhan D614G, Delta and Omicron. While Wuhan D614G was neutralized in-vitro by Bamlanivimab, Casirivimab and Imdevimab, Omicron was resistant to these monoclonal antibodies.

Conclusions

These findings confirm substantial immune evasion of Delta and Omicron which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.17.22269201: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Samples were collected after informed consent from convalescent plasma donors (17) and vaccinees.
    IRB: The studies were approved by the Ethical Committee of University of Ulm and Ethical Committee II, Heidelberg University.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Then the inoculum was removed, cells were washed with PBS and fresh medium containing anti-VSV-G antibody (I1-hybridoma cells; ATCC no. CRL-2700) added to block remaining VSV-G carrying particles.
    anti-VSV-G
    suggested: (LSBio (LifeSpan Cat# LS-C132922-100, RRID:AB_10836195)
    Experimental Models: Cell Lines
    SentencesResources
    In brief, 293T cells (ATCC no. CRL-3216) were transfected with expression plasmids encoding SARS-CoV-2 spike variants Wuhan D614G (https://doi.org/10.1016/j.cell.2021.03.036), B.1.617.2 (https://doi.org/10.1126/science.abh1766), or B.1.1.529 (https://doi.org/10.1101/2021.12.12.472286) (kindly provided by Stefan Pöhlmann, Infection Biology Unit, German Primate Center, Göttingen, Germany) by Transit LT-1 (Mirus).
    293T
    suggested: None
    Pseudovirus Neutralization Assay: The pseudovirus neutralization experiments were performed as previously described (18) In brief, Vero E6 cells were seeded in 96-well plates one day prior (6,000 cells/well, 2.5%
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Results are given as serum dilution on cell resulting in 50% pseudovirus neutralization (NT50), calculated by nonlinear regression ([Inhibitor] vs. normalized response – Variable slope) in GraphPad Prism Version 9.1.1.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software, San Diego, California USA,
    GraphPad
    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.

    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.

  2. Version published to 10.1101/2022.01.17.22269201v1 on medRxiv