Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants

Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in…

• OS
  Ohio State University
• NI
  National Institutes of Health

  Awards: R01 HD095881, UH2 AI171611, U54CA260582
• CF
  Center for Clinical and Translational Science, Ohio State University
• CO
  College of Veterinary Medicine, Ohio State University
• NC
  National Cancer Institute

  Award: U54CA260582
• NI
  National Institute of Allergy and Infectious Diseases

  Award: U01 AI173348