Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants

  1. Satoshi Ikegame
  2. Mohammed N. A. Siddiquey
  3. Chuan-Tien Hung
  4. Griffin Haas
  5. Luca Brambilla
  6. Kasopefoluwa Y. Oguntuyo
  7. Shreyas Kowdle
  8. Ariel Esteban Vilardo
  9. Alexis Edelstein
  10. Claudia Perandones
  11. Jeremy P. Kamil
  12. Benhur Lee

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Abstract

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC 90 ) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.

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  1. Rapid Reviews Infectious Diseases

    Mario Cazzola, Maria Gabriella Matera

    Review 2: "Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants"

    This study reports antibodies generated from Sputnik V vaccination exhibit less neutralizing activity against B.1.351 and E484K variants than wildtype and B.1.1.7. Reviewers deem these findings informative, but caution more standard assays and clinical studies are necessary.

  2. Rapid Reviews Infectious Diseases

    Alexander Mentzer

    Review 1: "Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants"

    This study reports antibodies generated from Sputnik V vaccination exhibit less neutralizing activity against B.1.351 and E484K variants than wildtype and B.1.1.7. Reviewers deem these findings informative, but caution more standard assays and clinical studies are necessary.

  4. Version published to 10.1101/2021.03.31.21254660v3 on medRxiv
  5. ScreenIT

    SciScore for 10.1101/2021.03.31.21254660: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Malbrán, Argentina) were approved by the Research Ethics Committee of its Unidad Operativa Centro de
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: Vero-CCL81 TMPRSS2, HEK 293T-hACE2 (clone 5-7), and 293T-hACE2-TMPRSS2 (clone F8-2) cells were described previously (Oguntuyo et al., 2021), and were maintained in DMEM + 10%FBS.
    HEK 293T-hACE2
    suggested: None
    The HEK 293T-hACE2-TMPRSS2 cells were plated on collagen coated plates or dishes.
    HEK 293T-hACE2-TMPRSS2
    suggested: None
    Rescued viruses were amplified in Vero-CCL81 TMPRSS2 cells (Oguntuyo et al., 2021), then titered and used for the assay.
    Vero-CCL81 TMPRSS2
    suggested: None
    S amino acids 319 – 541 (corresponding to the RBD domain) sequence were C-terminally fused to the Fc region of human IgG1 (220 – 449 aa of P0DOX5.2) Generation of recombinant Sendai virus from cDNA: 2×10E5 BSR-T7 cells per well were seeded onto 6-well cluster plates.
    BSR-T7
    suggested: CCLV Cat# CCLV-RIE 0583, RRID:CVCL_RW96)
    For VSV-CoV2 titration, 5 x 10E4 293T-hACE2-TMPRSS2 cells per well were seeded onto a collagen-coated 96 well plate.
    293T-hACE2-TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    Inhibition curves were generated using Prism 8.4.3 (GraphPad Software) with ‘log (inhibitor) vs normalized response - variable slope’ settings.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    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

    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.

  6. Version published to 10.1101/2021.03.31.21254660v2 on medRxiv
  7. Version published to 10.1101/2021.03.31.21254660v1 on medRxiv