Abstract
Conventional neutralizing enzyme-linked immunosorbent assay (ELISA) systems for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimic the protein-protein interaction between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD). However, an easy and rapidly adaptative ELISA-based system for testing neutralizing antibodies against upcoming SARS-CoV-2 variants is urgently needed. In this study, we closed this gap by developing a tANCHOR-cell-based RBD neutralization assay that avoids time-consuming protein expression and purification followed by coating on ELISA plates. This cell-based assay can be rapidly adopted to monitor neutralizing antibodies (NAbs) against upcoming SARS-CoV-2 variants. We show that the results obtained with the tANCHOR-cell-based assay system strongly correlate with commercially available surrogate assays for testing NAbs. Moreover, this technique can directly measure binding between cell-surface-exposed RBDs and soluble ACE2. With this technique, the degree of antibody escape elicited by emerging SARS-CoV-2 variants in current vaccination regimens can be determined rapidly and reliably.