Study of SARS-CoV-2 Spike Protein Wild-Type and the Variants of Concern Real-Time Interactions with Monoclonal Antibodies and Convalescent Human Serum.

The spike (S) protein and its receptor-binding domain (RBD) of the coronavirus SARS-CoV-2 have been continually evolving, yielding the majority of significant missense mutations and new variants of concern. In this study, we examined how monoclonal antibodies against RBD (mAbs-SCoV2-RBD) and polyclonal antibodies present in convalescent human serum specifically interact with the S protein of wild-type and SARS-CoV-2 variants of concern (VOCs) in real time and how this can be reflected through surface mass density. Moreover, we combined two distinct, label-free measurement techniques: one based on changes in surface electromagnetic waves after reflection from the surface, and the other on changes in acoustic waves. The results demonstrated that dry surface mass density (Γ SE ) of mAbs-SCoV2-RBD attached to the RBD of the S protein decreases three-fold, from 148 ng/cm 2 to 46 ng/cm 2 , due to the B.1.351 or so-called beta mutation of coronavirus and its S protein (SCoV2-β). Consequently, the obtained wet mass Γ QCM-D resulted in values two times lower, from 319 ng/cm 2 to 158 ng/cm 2 , and the hydration of mAbs-SCoV2-RBD/SCoV2-β immune complex was 70.88%. Conversely, when polyclonal antibodies present in convalescent human serum form immune complexes with the S protein of SARS-CoV-2 variants of concern, the Γ SE decreased from 279 ng/cm 2 to 249 ng/cm 2 , and Γ QCM-D from 1545 ng/cm 2 to 1366 ng/cm 2 . These results can give insights into the differences between the interaction of monoclonal and polyclonal antibodies with SARS-CoV-2 VOCs.