Evaluation of a Surrogate Enzyme-Linked Immunosorbent Assay–Based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cPass Neutralization Antibody Detection Assay and Correlation With Immunoglobulin G Commercial Serology Assays

Abstract

Context: Emerging evidence shows correlation between the presence of neutralization antibodies (nAbs) and protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently available commercial serology assays lack the ability to specifically identify nAbs. An ELISAbased nAb assay (GenScript cPass neutralization antibody assay) has recently received emergency use authorization from the Food and Drug Administration (FDA). Objective: To evaluate the performance characteristics of this assay and compare and correlate it with the commercial assays that detect SARS-CoV-2 specific IgG. Design: Specimens from SARS-COV-2 infected patients (n=124), healthy donors obtained pre-pandemic (n=100), and from patients with non-COVID (coronavirus disease 2019) respiratory infections (n=92) were analyzed using this assay. Samples with residual volume were also tested on three commercial serology platforms (Abbott, EUROIMMUN, Siemens). Twenty-eight randomly selected specimens from patients with COVID-19 and 10 healthy controls were subjected to a Plaque Reduction Neutralization Test (PRNT). Results: The cPass assay exhibited 96.1% (95% CI, 94.9%–97.3%) sensitivity (at >14 days post- positive PCR), 100% (95% CI, 98.0%–100.0%) specificity and zero cross-reactivity for the presence of non- COVID respiratory infections. When compared to the plaque reduction assay, 97.4% (95% CI, 96.2%–98.5%) qualitative agreement and a positive correlation (R2 =0.76) was observed. Comparison of IgG signals from each of the commercial assays with the nAb results from PRNT/cPass assays displayed >94.7% qualitative agreement and correlations with R2=0.43/0.68 (Abbott), R2=0.57/0.85 (EUROIMMUN) and R2=0.39/0.63 (Siemens), respectively. Conclusions: The combined data support the use of cPass assay for accurate detection of the nAb response. Positive IgG results from commercial assays associated reasonably with nAbs presence and can serve as a substitute.

Detection of neutralizing antibodies against SARS-CoV-2 by using a commercial surrogate virus neutralization ELISA: can it substitute the classical neutralization test?

“…For the two tested Euroimmun ELISAs, but not the Wantai ELISA, high ratios were predictive of the presence of neutralizing antibodies in the sample. The Euroimmun S1 IgG ELISA was previously shown to have a moderate correlation with PRNT (R 2 =0.46 to 0.57) [13, 20], in line with the data from our study (R 2 =0.46). Furthermore, the Euroimmun S1 IgG ELISA ratios and GenScript sVNT results showed a similar correlation with PRNT titers in our study.…”

“…Previous studies have described a moderate to good correlation of GenScript sVNT results with antibody titers measured by PRNT [6,[11][12][13]. However, in some of these studies the correlation with PRNT has been assessed by using IC50 values determined by sVNT rather than by using the direct signal output of the GenScript sVNT, which is defined as percent of inhibition.…”

Quantitative SARS-CoV-2 Spike Antibody Response in COVID-19 Patients Using Three Fully Automated Immunoassays and a Surrogate Virus Neutralization Test

“…With the widespread use of vaccines and therapeutics, longitudinal detection and quantification of antibody responses associated with neutralization becomes increasingly important [12,13]. The SARS-CoV-2 surrogate virus neutralization test (sVNT) (GenScript, Netherlands) is currently available for detecting neutralizing antibodies targeting the RBD based on antibody-mediated blockage of the interaction between the ACE2 receptor and SARS-CoV-2 RBD [14]. To date, limited data are available correlating quantitative SARS-CoV-2 S protein antibody responses with sVNT results [15].…”

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

“…There is growing, but still limited, information available on immunity against the viral variants conferred by natural infection with the authentic SARS-CoV-2 strain or by the mRNA COVID-19 vaccines. Using samples collected during the COVID-19 pandemic, most of them before the documented introduction of the variants in the jurisdiction of Puerto Rico [26,28], we attempted to compare the kinetics of the nAbs response in the context of individuals with naturally acquired infection (pre-exposed) and unexposed individuals, following vaccination, via a widely used sVNT detecting RBD-targeting antibodies [26,[29][30][31].…”