Neutralization of SARS-CoV-2 Variants by rVSV-ΔG-Spike-Elicited Human Sera

  1. Yfat Yahalom-Ronen
  2. Noam Erez
  3. Morly Fisher
  4. Hadas Tamir
  5. Boaz Politi
  6. Hagit Achdout
  7. Sharon Melamed
  8. Itai Glinert
  9. Shay Weiss
  10. Inbar Cohen-Gihon
  11. Ofir Israeli
  12. Marina Izak
  13. Michal Mandelboim
  14. Yoseph Caraco
  15. Noa Madar-Balakirski
  16. Adva Mechaly
  17. Eilat Shinar
  18. Ran Zichel
  19. Daniel Cohen
  20. Adi Beth-Din
  21. Anat Zvi
  22. Hadar Marcus
  23. Tomer Israely
  24. Nir Paran

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Abstract

The emergence of rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability of vaccines and therapeutic antibodies to provide immunity. These variants contain mutations of specific amino acids that might impede vaccine efficacy. BriLife® (rVSV-ΔG-spike) is a newly developed SARS-CoV-2 vaccine candidate currently in phase II clinical trials. It is based on a replication-competent vesicular stomatitis virus (VSV) platform. The rVSV-ΔG-spike contains several spontaneously acquired spike mutations that correspond to SARS-CoV-2 variants’ mutations. We show that human sera from BriLife® vaccinees preserve comparable neutralization titers towards alpha, gamma, and delta variants and show less than a three-fold reduction in the neutralization capacity of beta and omicron compared to the original virus. Taken together, we show that human sera from BriLife® vaccinees overall maintain a neutralizing antibody response against all tested variants. We suggest that BriLife®-acquired mutations may prove advantageous against future SARS-CoV-2 VOCs.

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  1. Version published to 10.3390/vaccines10020291
  2. Version published to 10.1101/2021.11.22.21266673v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.22.21266673: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All convalescent volunteers gave their informed consent to the National Blood services of Magen David Adom.
    IRB: The study was approved by the ethics committee of the Israeli Ministry of Health (0083-20-WOMC)[20].
    Sex as a biological variablenot detected.
    RandomizationSamples: Serum samples of BriLife® vaccinees were obtained from participants in a randomized, multi-center, placebo-controlled, dose-escalation phase II of an ongoing clinical trial, aimed to evaluate the safety, immunogenicity and potential efficacy of BriLife®, an rVSV-SARS-CoV-2-S vaccine (IIBR-100) in Adults (ClinicalTrials.gov - NCT04608305).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells: Vero clone E6 cells (Vero E6, ATCC CRL-1586(tm)) were grown in growth medium [Dulbecco’s Modified Eagle’s Medium (DMEM) containing 10% fetal bovine serum (FBS), MEM nonessential amino acids (NEAA), 2 mM L-glutamine, 100 Units/ml penicillin, 0.1 mg/ml streptomycin, 12.5 Units/ml nystatin (P/S/N), all from Biological Industries, Israel].
    Vero clone E6
    suggested: None
    Calu3 cells (ATCC HTB-55) were grown in growth medium RPMI supplemented with 10% fetal bovine serum (FBS), MEM non-essential amino acids, 2 mM L-glutamine, 100 units per ml penicillin and 1% Na-pyruvate.
    Calu3
    suggested: ATCC Cat# HTB-55, RRID:CVCL_0609)
    Recombinant Vesicular Stomatitis Virus Indiana serotype (rVSV-WT) was propagated in Vero cells [1].
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    All virus stocks were tittered on Vero E6 cells by plaque assay as previously described [1].
    Vero E6
    suggested: RRID:CVCL_XD71)
    Recombinant DNA
    SentencesResources
    Sera from BriLife® vaccinees or COVID-19 convalescent patients were heat inactivated (HI) (56 °C for 30 min), then diluted in twofold serial dilutions (between 1:20 and 1:1280) in 300 µl of infection medium, mixed with 300 µl of either 300 pfu/ml of SARS-CoV-2 original virus, each variant (alpha, beta, gamma or delta), or rVSV-WT, and incubated at 37 °C, 5% CO2 for 1 h.
    rVSV-WT
    suggested: None
    Software and Algorithms
    SentencesResources
    The plaques in each well were numbered, and the serum dilution that neutralizes 50% of the virions (NT50) was calculated using GraphPad Prism 6 software (GraphPad Software Inc.).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04608305RecruitingEvaluate the Safety, Immunogenicity and Potential Efficacy o…

    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

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  4. Version published to 10.1101/2021.11.22.21266673v1 on medRxiv