A generalized framework to identify SARS-CoV-2 broadly neutralizing antibodies
Monoclonal antibodies (mAbs) targeting the SARS-CoV-2 receptor-binding domain (RBD) showed high efficacy in the prevention and treatment of COVID-19. However, the rapid evolution of SARS-CoV-2 has rendered all clinically authorized mAbs ineffective and continues to stymie the development of next-generation mAbs. Consequently, the ability to identify broadly neutralizing antibodies (bnAbs) that neutralize both current and future variants is critical for successful antibody therapeutic development, especially for newly emerged viruses when no knowledge about immune evasive variants is available. Here, we have developed a strategy to specifically select for potent bnAbs with activity against both existing and prospective SARS-CoV-2 variants based on accurate viral evolution prediction informed by deep mutational scanning (DMS). By adopting this methodology, we increased the probability of identifying XBB.1.5-effective SARS-CoV-2 bnAbs from ~1% to 40% if we were at the early stage of the p