Résumé
BACKGROUND/CONTEXT: Monoclonal antibodies (mAbs) and mAbs-based drugs are a therapeutic opportunity to treat several viral infections, including SARS-CoV-2. However, the ability of SARS-CoV-2 to mutate has led to the appearance of many variants, with mutations capable of abolishing the binding of many mAbs, highlighting the need for identifying new mAbs able to bind emerging variants of concern (VOCs). In this work several mAbs against SARS-CoV-2 Spike protein were generated using the phage display approach. The mAbs were characterized for their affinity and binding properties by ELISA and SPR. The experiments were initially performed using SARS-CoV-2 Wuhan and Omicron strains. Two promising mAbs candidates were selected; they are able to recognize very efficiently the infected cells expressing the Spike proteins on their surface. We next aimed to better characterize these two anti-SARS-CoV2 mAbs by performing epitope mapping experiments. Information on antibody epitopes is important to better assess their capacity to target different viral strains, and possibly new emerging VOCs; mAbs that bind to conserved epitopes are usually broadly reactive and show a high therapeutic potential.NEED FOR ISIDORe SERVICES: We requested ISIDORe services to take advantage of the high-capacity screening platforms integrated into EU-OPENSCREEN throughout Europe. They provide unique expertise in antibody characterization using multiple experimental approaches, including computational simulations. They also have a wealth of tools and biological material for characterizing the recognition of multiple VOCs by mAbs.METHODS/DESCRIPTION OF ISIDORe SERVICE(S): ISIDORe services allowed to in-depth characterize the two selected anti-SARS-CoV-2 mAbs. Epitope mapping studies were performed based on loss of binding to SARS-CoV-2 mutants/variants and SPR cross-competition. The experimental results guided computational analysis subsequently used to build structural models of mAb-antigen complexes. RESULTS: ISIDORe services led to the identification of one mAb able to bind all VOCs and mutants tested; the results suggest that its epitope may be located in a highly conserved RBD region, making it an ideal candidate as a therapeutic agent to target SARS-CoV-2 current, and possibly future, VOCs. CONCLUSION: The highly efficient antibody services provided by ISIDORe allowed to identify a “pan” anti-SARS-CoV-2 mAb able to target cells infected by different VOCs. The therapeutic potential of this mAb might be exploited by using it in a full-length format as well as by generating mAb-derived molecules for the development of different mAb-based therapeutic approaches against SARS-CoV-2 infection.