[slides and audio] Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

The study investigates the impact of the SARS-CoV-2 Omicron variant on the effectiveness of vaccines and antibody-based therapeutics. The Omicron variant, which contains 37 amino acid substitutions in the spike protein, particularly 15 in the receptor-binding domain (RBD), poses a significant challenge to existing defenses. The research finds that the Omicron RBD binds more strongly to human and mouse ACE2 receptors compared to the Wuhan-Hu-1 RBD, leading to reduced neutralizing activity in plasma from convalescent individuals and vaccinated individuals. Most monoclonal antibodies targeting the RBD lose their neutralizing activity against Omicron, with only a few retaining potency, including the ACE2-mimicking S2K146 antibody. Additionally, a subset of broadly neutralizing sarbecovirus monoclonal antibodies can neutralize Omicron by recognizing antigenic sites outside the RBD. These findings highlight the need for new vaccines and therapies that target conserved epitopes to combat the ongoing pandemic and future zoonotic spillovers.The study investigates the impact of the SARS-CoV-2 Omicron variant on the effectiveness of vaccines and antibody-based therapeutics. The Omicron variant, which contains 37 amino acid substitutions in the spike protein, particularly 15 in the receptor-binding domain (RBD), poses a significant challenge to existing defenses. The research finds that the Omicron RBD binds more strongly to human and mouse ACE2 receptors compared to the Wuhan-Hu-1 RBD, leading to reduced neutralizing activity in plasma from convalescent individuals and vaccinated individuals. Most monoclonal antibodies targeting the RBD lose their neutralizing activity against Omicron, with only a few retaining potency, including the ACE2-mimicking S2K146 antibody. Additionally, a subset of broadly neutralizing sarbecovirus monoclonal antibodies can neutralize Omicron by recognizing antigenic sites outside the RBD. These findings highlight the need for new vaccines and therapies that target conserved epitopes to combat the ongoing pandemic and future zoonotic spillovers.