Therapeutic Intervention of an Intranasally Administered Monoclonal Antibody Targeting the SARS-CoV-2 Omicron Spike Protein Against SARS-CoV-2 Omicron Infection in Mice.

SARS-CoV-2 has evolved into several variants of concern, with Omicron and its subvariants currently being the most prevalent. Previously, we developed a mouse monoclonal antibody (m1E3H12 mAb) specific to the receptor binding domain of SARS-CoV-2 Omicron spike protein, and the mAb showed neutralizing activity against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB. Here, we showed that the mAb provided protection against SARS-CoV-2 Omicron infection in K18-hACE2 transgenic mice when administered intranasally. The mAb treatment reduced viral loads in both the brain and lungs. Additionally, the elevated levels of RANTES (CCL5) and MIP-3 alpha (CCL20) in the brain following SARS-CoV-2 Omicron infection showed a decreasing trend after mAb treatment. Therefore, we conclude that our mAb specific to SARS-CoV-2 Omicron spike protein has the potential to be applied as therapeutics against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB.