ABSTRACT
Background: There is a need for automated, high throughput assays to quantify immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study assessed the combined utility of the Roche assays, Elecsys(R) Anti-SARS-CoV-2 S (ACOV2S) and Elecsys Anti-SARS-CoV-2 (ACOV2N) using samples from the 2019-nCoV vaccine (mRNA-1273, Spikevax) phase 2 trial (NCT04405076). Methods: Samples from 593 healthy participants in two age cohorts (18-54 years and [≥]55 years), who received two injections with either placebo (n=198) or mRNA-1273 at a dose of either 50 [≥]g (n=197) or 100 [≥]g (n=198), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results were used to assess the humoral response to vaccination in different clinical trial subgroups and were compared to a live virus microneutralization assay. Sample panels from patients with evidence of previous or concomitant infection (as identified using ACOV2N) or with an inconsistent antibody response pattern were analyzed separately. Results: Receptor-binding domain (RBD)-specific antibodies were readily detectable by ACOV2S for the vast majority of participants (174/189 [50 [≥]g dose group] and 178/192 [100 [≥]g]) at the first time point of assessment, with non-converters predominantly older in age. Complete seroconversion for all participants was observed at the subsequent timepoint (Day 29) and before administration of the second dose of vaccine. Two weeks after the first vaccine dose (Day 15), geometric mean concentration (GMC) of antibody levels were 1.37-fold higher in the 100 [≥]g compared with the 50 [≥]g dose group; this difference reduced to 1.09-fold two weeks after the second dose (Day 43). In both the 50 [≥]g and 100 [≥]g dose groups, a more pronounced response was observed in the younger versus the older age group on Day 15 (2.49-fold and 3.94-fold higher GMC, respectively) and Day 43 (1.35-fold and 1.50-fold higher GMC). Few subjects had a previous or concomitant natural SARS-CoV-2-infection (n=8). Vaccination of pre-infected individuals boosted the immune response to very high ACOV2S results compared to infection-naive vaccine recipients. ACOV2S measurements were strongly correlated with those from the live microneutralization assay (Pearson's r=0.779; p<0.0001) and good qualitative agreement was achieved (100% positive and 91.8% negative percentage agreement; 90.0% positive and 100% negative predictive value). Conclusion: The results from this study confirmed that ACOV2S is a highly valuable assay for the tracking of vaccine-related immune responses. Combined application with ACOV2N enables serologic monitoring for breakthrough infection or stratification of previous natively-infected individuals. The adaptive measuring range and high resolution of ACOV2S allows for the early identification of seroconversion as well as for resolution of very high titers and detection of longitudinal differences between age and dose groups. Additionally, good correlation of ACOV2S with live virus microneutralization indicates the utility of ACOV2S as a reliable estimate of neutralization capacity in routine diagnostic settings.
Subject(s)
COVID-19 , Breakthrough Pain , Coronavirus Infections , Severe Acute Respiratory SyndromeABSTRACT
BackgroundThe 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(R) Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461). MethodsSamples from 30 healthy participants, aged 18-55 years, who received two injections with mRNA-1273 at a dose of 25 g (n=15) or 100 g (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). ResultsRBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 g dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27-7.48-fold higher in the 100 g compared with the 25 g dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearsons 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). ConclusionThe 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.