Broad Neutralizing Activity of Monoclonal Antibodies Against the Omicron Variants Isolated From Patients With Early Severe Acute Respiratory Syndrome Coronavirus-2.

Since its emergence in 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic driven by rapid mutation and high transmissibility. Current therapeutic strategies may not effectively address the continuously evolving mutant strains, underscoring the need for treatments with broad neutralizing activity. Two monoclonal antibodies (mAbs): SR-23 and CS-42, isolated from convalescent patients infected with SARS-CoV-2 during the early phase of the 2020 pandemic, demonstrated significant neutralizing activities against a variety of variants. Specifically, SR-23 exhibited neutralizing activity against BA.5 and XBB1.5, whereas CS-42 showed efficacy against Delta, BA.1, and BA.2 variants. In addition, combining the two mAbs demonstrated improved neutralization activity. Cryo-electron microscopy (cryo-EM) structural analysis revealed that SR-23 and CS-42 bind to nonoverlapping epitopes on the SARS-CoV-2 spike protein. Furthermore, both antibodies exhibited strong therapeutic effects in K18-hACE2 mice infected with D614G, BA.2, and XBB.1.5. These findings provide insights into the development of antibody-based therapeutics targeting emerging Omicron variants and suggest that combined administration could broaden neutralizing activity.