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

Simon Jochum, Imke Kirste, Sayuri Hortsch, Veit Peter Grunert, Holly Legault, Udo Eichenlaub, Basel Kashlan, Rolando Pajon, Simon Jochum, Imke Kirste, Sayuri Hortsch, Veit Peter Grunert, Holly Legault, Udo Eichenlaub, Basel Kashlan, Rolando Pajon

Abstract

Background: 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.

Keywords: COVID-19; ELISA; SARS-CoV-2; quantitative serology; vaccination.

Conflict of interest statement

SJ, IK, SH, VPG and UE are employees of Roche Diagnostics. BK is an employee of PPD, Inc. HL and RP are employees of Moderna, Inc. The authors declare that this study received funding from Roche Diagnostics GmbH. The funder was involved in the study design, analysis, interpretation of data, the writing of this article and the decision to submit it for publication.

Copyright © 2022 Jochum, Kirste, Hortsch, Grunert, Legault, Eichenlaub, Kashlan and Pajon.

Figures

Figure 1
Figure 1
Time-dependent antibody responses as measured by the ACOV2S. Reverse cumulative distribution curves allow for comparison of ACOV2S-measured antibody level distributions between dose groups (A) and visit days (B). Red vertical line indicates reactivity cut-off (0.8 U/mL).
Figure 2
Figure 2
Time course of ACOV2S-measured antibody levels following mRNA-1273 vaccination and native infection. Antibody levels following vaccination are shown in (A, B); dotted grey vertical lines indicate time of vaccination, administered at Days 1 and 29. Antibody levels in samples post PCR-confirmed SARS-CoV-2 infection are shown in (C, D). Box plots show the individual readouts (black dots) and, 25th, 50th, and 75th percentiles (black box). Red horizontal line indicates reactivity cut-off (0.8 U/mL).
Figure 3
Figure 3
Comparison of ACOV2S and ELISA. Passing–Bablok regression fit (log-scale) for the comparison with RBD ELISA is shown in (A), and with S-2P ELISA in (B) Red dotted line shows ACOV2S reactivity cut-off. The shaded area represents the 95% confidence interval for the fitted curve. Dots and triangles represent individual samples; filled dots or triangles represent samples within the measuring range for the ACOV2S assay. Time courses of antibody responses measured by RBD ELISA and S-2P ELISA compared to ACOV2S are shown in (C, D), respectively. Dotted grey vertical lines show when vaccination injections were administered at Days 1 and 29. Red horizontal line shows ACOV2S reactivity cutoff, and the black dashed horizontal line represents the lower end of the ACOV2S measuring range. Box plots show the individual readouts (dots) and, 25th, 50th, and 75th percentiles (box). Time-dependent geometric mean concentrations and geometric mean titers across vaccine dose groups of ACOV2S levels vs RBD ELISA and S-2P ELISA are shown in (E, F), respectively. Shaded areas indicate 95% confidence intervals.
Figure 4
Figure 4
Comparison of ACOV2S and neutralization assays. Passing–Bablok regression fit (log-scale) of ACOV2S with nLUC80 is shown in (A), PsVNA50 in (B) and PRNT80 in (C). Red dotted line shows ACOV2S reactivity cut-off. The shaded area represents the 95% confidence interval for the fitted curve. Dots or crosses show individual sample readouts. Filled dots or triangles represent samples within the measuring range for both ACOV2S and respective comparator assay. Overlaid table shows the qualitative agreement between Elecsys ACOV2S and comparator assays.

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