Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

  1. Benjamin L. Sievers
  2. Saborni Chakraborty
  3. Yong Xue
  4. Terri Gelbart
  5. Joseph C. Gonzalez
  6. Arianna G. Cassidy
  7. Yarden Golan
  8. Mary Prahl
  9. Stephanie L. Gaw
  10. Prabhu S. Arunachalam
  11. Catherine A. Blish
  12. Scott D. Boyd
  13. Mark M. Davis
  14. Prasanna Jagannathan
  15. Kari C. Nadeau
  16. Bali Pulendran
  17. Upinder Singh
  18. Richard H. Scheuermann
  19. Matthew B. Frieman
  20. Sanjay Vashee
  21. Taia T. Wang
  22. Gene S. Tan

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Abstract

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

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  1. Version published to 10.1126/scitranslmed.abn7842
  2. ScreenIT

    SciScore for 10.1101/2021.12.30.21268540: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Clinical cohorts and samples: Characterization of these samples at Stanford was performed under a protocol approved by the Institutional Review Board of Stanford University (protocol
    Consent: All participants gave written informed consent, and all study procedures were approved by the Institutional Review Board of Stanford University (IRB-55619).
    Sex as a biological variableThere are 28 males and 29 females in the study.
    RandomizationStanford Lambda cohort: 120 participants were enrolled in a phase 2 randomized controlled trial of Peginterferon Lambda-1a (Lambda, NCT04331899) Inclusion/exclusion criteria and the study protocol for the trial have been published(12).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    After poly-D-lysine treatment, plates were washed three times with sterile water and then seeded with 1.5e6 cells of HEK 293T per well.
    HEK 293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    Prior to infection, Vero E6-TMPRSS2-T2A-ACE2 cells were washed with 1X PBS and then 50 μL of the incubated pseudotyped particles and patient plasma mixture was then transferred from the U-bottom 96-well dilution plates onto the monolayer and placed into an incubator at 37°C and 5% CO2.
    Vero E6-TMPRSS2-T2A-ACE2
    suggested: None
    Recombinant DNA
    SentencesResources
    SARS-CoV-2 spike variant spike construction: The WT SARS-CoV-2 spike gene was previously amplified with KOD Xtreme Hot Start DNA polymerase (Millipore) using cDNA from SARS-CoV-2/human/USA/WA-CDC-WA1/2020 (GenBank MN985325.1) and cloned into pCC1BAC-his3 vector (27).
    pCC1BAC-his3
    suggested: None
    50 fmol of each amplicon and 15 fmol of YCP/BAC vector were covalently joined using standard Gibson assembly reaction (NEB), transformed into E.coli DH10B competent cells (Thermo Fisher), and plated on LB medium with 12.5 mg/ml chloramphenicol.
    YCP/BAC
    suggested: None
    Lastly, the spike genes lacking the cytoplasmic domain by deleting the last 18 amino acides were then cloned into the pCAGGS expression vector.
    pCAGGS
    suggested: RRID:Addgene_127347)
    After 24 hours (h), cells were transfected with 1 µg of pCAGGS-SΔ18 per well using Lipofectamine 2000 transfection reagent (ThermoFisher, Cat. No., 11668019).
    pCAGGS-SΔ18
    suggested: None
    A non-linear curve and the half-maximal pseudoparticle neutralization titer (pNT50) were generated using GraphPad Prism.
    pNT50
    suggested: None
    Software and Algorithms
    SentencesResources
    E.coli transformants were verified to contain correct mutations using PCR and Sanger sequencing (GeneWiz).
    GeneWiz
    suggested: (GENEWIZ, RRID:SCR_003177)
    A non-linear curve and the half-maximal pseudoparticle neutralization titer (pNT50) were generated using GraphPad Prism.
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04331899CompletedSingle-Blind Study of a Single Dose of Peginterferon Lambda-…

    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 10.1101/2021.12.30.21268540v1 on medRxiv