Development of a neutralization monoclonal antibody with a broad neutralizing effect against SARS-CoV-2 variants

Abstract

Abstract Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the effectiveness of current therapeutic regimens. Here, we aimed to develop a potent and broad SARS-CoV-2 antibody therapeutic by screening a scFv library with the spike protein receptor-binding domain (RBD) via phage display. Methods SKAI-DS84 was identified through phage display, and it underwent pseudovirus neutralization assays, authentic virus neutralization assays, and in vivo neutralization efficacy evaluations. Furthermore, surface plasmon resonance (SPR) analysis was conducted to assess the antibody's physical characteristics and measure its affinity. Results The selected clones were converted to human IgG, their binding affinities with the variant RBDs were confirmed, and SKAI-DS84 was selected. Using pseudoviruses, we confirmed its high neutralizing effects against SARS-CoV-2 wild-type, B.1.617.2, B.1.1.52, and subvariants. SKAI-DS84 showed potent neutralizing activity against various SARS-CoV-2 variants. We also tested the neutralizing effect of SKAI-DS84 on authentic viruses in vivo and observed a reduction in viral replication and improved lung pathology. We performed binding and epitope mapping experiments to understand the mechanism underlying neutralization and identified quaternary epitopes formed by the interaction between the RBDs as the target for SKAI-DS84. Conclusions Overall, this study highlights the potential of SKAI-DS84 as a neutralizing antibody against broadly SARS-CoV-2 and its variants.