Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines

  1. Yannic C. Bartsch
  2. Xin Tong
  3. Jaewon Kang
  4. María José Avendaño
  5. Eileen F. Serrano
  6. Tamara García-Salum
  7. Catalina Pardo-Roa
  8. Arnoldo Riquelme
  9. Yongfei Cai
  10. Isabella Renzi
  11. Guillaume Stewart-Jones
  12. Bing Chen
  13. Rafael A. Medina
  14. Galit Alter

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein–specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein–specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein–specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.

Article activity feed

  1. Version published to 10.1126/scitranslmed.abn9243
  2. ScreenIT

    SciScore for 10.1101/2021.12.24.21268378: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: For the CoronaVac study informed written consent was obtained under protocol 200829003 which was reviewed and approved by the Scientific Ethics Committee at Pontificia Universidad Católica de Chile (PUC).
    IRB: For the CoronaVac study informed written consent was obtained under protocol 200829003 which was reviewed and approved by the Scientific Ethics Committee at Pontificia Universidad Católica de Chile (PUC).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    IgG subclass, isotype and FcγR binding: Antigen specific antibody subclass and isotypes, and FcγR binding was analyzed by Luminex multiplexing.
    IgG subclass ,
    suggested: None
    Antigen
    suggested: None
    Unbound antibodies were washed away and subclasses, isotypes were detected with a respective PE-conjugated antibody (anti-human IgG1, IgG2, IgG3, IgG4, IgM or IgA1 all SouthernBiotech, AL, USA) at a 1:100 dilution.
    anti-human IgG1
    suggested: None
    IgG2
    suggested: None
    IgG3, IgG4
    suggested: None
    IgA1
    suggested: (LSBio (LifeSpan Cat# LS-C68444-100, RRID:AB_1649687)
    Experimental Models: Cell Lines
    SentencesResources
    Stabilized (hexa-pro) spike of D614G or respective variants was produced in HEK293 cells.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04283461Active, not recruitingSafety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1…

    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.

  3. Version published to 10.1101/2021.12.24.21268378v1 on medRxiv