Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• The SARS-CoV-2 Omicron variant possesses numerous spike protein mutations, raising concerns about vaccine and therapeutic efficacy.
• Omicron's receptor-binding domain (RBD) exhibits altered binding characteristics, including enhanced affinity for human ACE2 and binding to mouse ACE2.

Approach:

• Assessed Omicron RBD binding affinity to human and mouse ACE2.
• Evaluated neutralizing activity of plasma from vaccinated and convalescent individuals against Omicron.
• Tested the in vitro neutralizing activity of various monoclonal antibodies (mAbs) against the Omicron variant.

Key Points:

• Omicron RBD binds human ACE2 with higher affinity and gains binding to mouse ACE2.
• Vaccinated and convalescent plasma showed significantly reduced neutralizing activity against Omicron.
• Most receptor-binding motif (RBM)-directed monoclonal antibodies lost activity, while some broadly neutralizing sarbecovirus mAbs retained potency.

Conclusions:

• Omicron represents a significant mutational shift in SARS-CoV-2, characterized by immune evasion and altered ACE2 binding.
• Broadly neutralizing sarbecovirus mAbs targeting conserved epitopes are essential for combating current and future coronavirus threats.