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

Cell Reports (May 2023)

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

Journal volume & issue: Vol. 42, no. 5
p. 112443

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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