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

doi:10.1016/j.celrep.2023.112443

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

Cell Rep. 2023 May 30;42(5):112443. doi: 10.1016/j.celrep.2023.112443. Epub 2023 Apr 18.

Authors

Panke Qu¹, Julia N Faraone², John P Evans², Yi-Min Zheng¹, Claire Carlin³, Mirela Anghelina⁴, Patrick Stevens⁴, Soledad Fernandez⁴, Daniel Jones⁵, Ashish R Panchal⁶, Linda J Saif⁷, Eugene M Oltz⁸, Baoshan Zhang⁹, Tongqing Zhou⁹, Kai Xu¹⁰, Richard J Gumina¹¹, Shan-Lu Liu¹²

Affiliations

¹ Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
² 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.
³ Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA.
⁴ Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
⁵ Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁶ Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁷ 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.
⁸ Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
⁹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁰ 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.
¹¹ 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.
¹² 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. Electronic address: liu.6244@osu.edu.

Abstract

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.

Keywords: CA.3.1; CH.1.1; CP: Immunology; CP: Microbiology; Omicron subvariants; XBB.1.5; fusogenicity; immune evasion; mAb S309; neutralizing antibody.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal*
Antibodies, Neutralizing*
Antibodies, Viral
Antibody Formation
Mutation / genetics
RNA, Messenger / genetics
Vaccines, Combined

Substances

Antibodies, Neutralizing
Antibodies, Monoclonal
RNA, Messenger
Vaccines, Combined
Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding