Neutralization, effector function and immune imprinting of Omicron variants

(RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent…

• HH
  Howard Hughes Medical Institute
• BW
  Burroughs Wellcome Fund
• UO
  University of Washington

  Award: T32GM007270
• FG
  Fast Grants
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: P01AI167966, 75N93022C00036, DP1AI158186, T32GM007270