Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants
Panke Qu,
Julia N. Faraone,
John P. Evans,
Yi-Min Zheng,
Claire Carlin,
Mirela Anghelina,
Patrick Stevens,
Soledad Fernandez,
Daniel Jones,
Ashish R. Panchal,
Linda J. Saif,
Eugene M. Oltz,
Baoshan Zhang,
Tongqing Zhou,
Kai Xu,
Richard J. Gumina,
Shan-Lu Liu
Affiliations
Panke Qu
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
Julia N. Faraone
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA
John P. Evans
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA
Yi-Min Zheng
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
Claire Carlin
Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA
Mirela Anghelina
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Patrick Stevens
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Soledad Fernandez
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Daniel Jones
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Ashish R. Panchal
Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Linda J. Saif
Center for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; Veterinary Preventive Medicine Department, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA; Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA
Eugene M. Oltz
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA
Baoshan Zhang
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Tongqing Zhou
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kai Xu
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA
Richard J. Gumina
Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA
Shan-Lu Liu
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA; Corresponding author
Summary: 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 CH.1.1 and CA.3.1 likely drive escape from class II neutralizing antibodies, whereas R346T and G339H mutations could confer the strong neutralization resistance of these two subvariants to S309-like antibodies. Overall, our results support the need for administration of the bivalent mRNA vaccine and continued surveillance of Omicron subvariants.
