Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity

  1. Priscilla Turelli
  2. María-Eugenia Zaballa
  3. Charlène Raclot
  4. Craig Fenwick
  5. Laurent Kaiser
  6. Isabella Eckerle
  7. Giuseppe Pantaleo
  8. Idris Guessous
  9. Silvia Stringhini
  10. Didier Trono

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

The rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics.

Methods

Convalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants.

Findings

Prior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants.

Interpretation

Moderately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination.

Funding

EPFL COVID Fund; private foundation advised by CARIGEST SA; Private Foundation of the Geneva University Hospitals; General Directorate of Health of the canton of Geneva, the Swiss Federal Office of Public Health.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.05.02.22274436: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants gave written informed consent and completed a questionnaire reporting on vaccination status and previous confirmed SARS-CoV-2 infections at the moment of providing a venous blood sample.
    IRB: The Geneva Cantonal Commission for Research Ethics approved this study (Project ID 2020-00881).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Immunoassays: Anti-SARS-CoV-2 antibodies in fresh serum samples were tested upon collection using two commercially-available immunoassays: the Roche Elecsys® anti-SARS-CoV-2 S immunoassay (Roche Diagnostics, Rotkreuz, Switzerland), detecting immunoglobulins (IgG/A/M) against the receptor binding domain of the virus spike (S) protein (#09 289 275 190, Roche anti-S); and the Roche Elecsys® anti-SARS-CoV-2 N immunoassay, detecting immunoglobulins (IgG/A/M) targeting the virus nucleocapsid (N) protein (#09 203 079
    Anti-SARS-CoV-2
    suggested: None
    anti-S)
    suggested: (Novus Cat# H00000191-M09, RRID:AB_536653)
    Briefly, 1:3 serial dilutions of sera were incubated 1 hour with the Spikes before ACE2 mouse Fc fusion protein (produced and purified as previously described10) was added and binding detected with an anti-mouse IgG-PE secondary antibody (OneLambda, Thermo Fisher Scientific).
    anti-mouse IgG-PE
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Viral stocks were prepared with the early isolates in EPISERF on VeroE6 or Calu-3 cells, aliquoted, frozen and titrated on VeroE6 cells.
    Calu-3
    suggested: KCLB Cat# 30055, RRID:CVCL_0609)
    The mix was then applied on VeroE6 cells and cytopathic effect detected 48hours later with Crystal violet staining.
    VeroE6
    suggested: None
    Recombinant DNA
    SentencesResources
    The Omicron Spike ectodomain was amplified by PCR and introduced by In-Fusion cloning into the nCoV-2P-F3CH2S plasmid, replacing the original wild-type Spike19.
    nCoV-2P-F3CH2S
    suggested: None
    Software and Algorithms
    SentencesResources
    Mutations found in other variants have either been cloned by PCR-mediated mutagenesis in the Wuhan codon-optimized ORF (Delta AY.4.2, Iota, Eta, Omicron BA.1.1), gene synthesis (Delta, Kappa, Lambda) or gBlocks assembly (Omicron BA.1).
    gBlocks
    suggested: (Gblocks, RRID:SCR_015945)
    Serum dilution response inhibition curves were generated using GraphPad Prism 8.3.0 NonLinear four parameter curve fitting analysis of the agonist versus response, and ED50% values extracted using an in-house script.
    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.

    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 10.1101/2022.05.02.22274436v1 on medRxiv