Clinical Utility of Elecsys Anti-SARS-CoV-2 S Assay in COVID-19 Vaccination: An Exploratory Analysis of the mRNA-1273 Phase 1 Trial

  1. Simon Jochum
  2. Imke Kirste
  3. Sayuri Hortsch
  4. Veit Peter Grunert
  5. Holly Legault
  6. Udo Eichenlaub
  7. Basel Kashlan
  8. Rolando Pajon

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Abstract

The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys ® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461).

Methods

Samples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50).

Results

RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but two participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels was 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson’s r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate–strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p ≤ 0.0001).

Conclusion

The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.

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  1. Version published to 10.3389/fimmu.2021.798117
  2. Version published to 10.1101/2021.10.04.21264521v4 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.10.04.21264521: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Informed written consent was originally obtained from all study participants in the context of the associated vaccine phase I study and the study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines.
    IRB: Approval was granted by the Advarra institutional review board for the phase 1 trial (18) and the diagnostic protocol under which the existing samples were tested.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement results are shown in U/mL, with the cut-off point defined as 0.80 U/mL to differentiate samples as reactive (≥ 0.80 U/mL) and non-reactive (< 0.80 U/mL) for SARS-CoV-2 RBD-specific antibodies.
    SARS-CoV-2
    suggested: None
    RBD-specific
    suggested: None
    Traceability of results to international BAU/mL: Of note, the assigned U/mL are equivalent to Binding Antibody Units (BAU)/mL as defined by the first World Health Organization (WHO) International Standard for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136).
    anti-SARS-CoV-2 immunoglobulin
    suggested: None
    Results from assays that target neutralizing antibodies, providing an estimate of vaccine-induced, antibody-mediated neutralizing activity, were also assessed.
    antibody-mediated neutralizing activity,
    suggested: None
    Statistical analysis: For each trial population and dosage group, ACOV2S-measured anti-RBD antibody levels are shown as boxplots (log-scale) for every measurement time point, with values outside the measuring range censored.
    anti-RBD
    suggested: None

    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: We detected the following sentences addressing limitations in the study:
    Limitations of our study include the small sample size as well as the lack of variation in time points available for analysis for some of the neutralization assays. The relatively short follow-up mitigates analysis of the ability of ACOV2S assay to determine the sustainability of antibody response. Further comparison studies using longer term follow-up and bigger samples sizes are warranted.

    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.

  4. Version published to 10.1101/2021.10.04.21264521v3 on medRxiv
  5. Version published to 10.1101/2021.10.04.21264521v1 on medRxiv
  6. Version published to 10.1101/2021.10.04.21264521v2 on medRxiv