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Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants

Panke Qu, Julia N. Faraone, John P. Evans, Xue Zou, Yi-Min Zheng, Claire Carlin, Joseph S. Bednash, Gerard Lozanski, Rama K. Mallampalli, Linda J. Saif, Eugene M. Oltz, Peter J. Mohler, Richard J. Gumina, View ORCID ProfileShan-Lu Liu
doi: https://doi.org/10.1101/2022.05.16.492158
Panke Qu
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
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Julia N. Faraone
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
3Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA
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John P. Evans
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
3Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA
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Xue Zou
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
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Yi-Min Zheng
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
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Claire Carlin
4Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA
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Joseph S. Bednash
5Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA
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Gerard Lozanski
6Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
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Rama K. Mallampalli
5Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA
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Linda J. Saif
7Center for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA
8Veterinary Preventive Medicine Department, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
9Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA
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Eugene M. Oltz
10Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA
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Peter J. Mohler
4Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA
11Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
12Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
13Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Richard J. Gumina
4Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA
12Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
13Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Shan-Lu Liu
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
9Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA
10Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA
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  • ORCID record for Shan-Lu Liu
  • For correspondence: liu.6244@osu.edu
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Summary

The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 17, 2022.
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Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants
Panke Qu, Julia N. Faraone, John P. Evans, Xue Zou, Yi-Min Zheng, Claire Carlin, Joseph S. Bednash, Gerard Lozanski, Rama K. Mallampalli, Linda J. Saif, Eugene M. Oltz, Peter J. Mohler, Richard J. Gumina, Shan-Lu Liu
bioRxiv 2022.05.16.492158; doi: https://doi.org/10.1101/2022.05.16.492158
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Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants
Panke Qu, Julia N. Faraone, John P. Evans, Xue Zou, Yi-Min Zheng, Claire Carlin, Joseph S. Bednash, Gerard Lozanski, Rama K. Mallampalli, Linda J. Saif, Eugene M. Oltz, Peter J. Mohler, Richard J. Gumina, Shan-Lu Liu
bioRxiv 2022.05.16.492158; doi: https://doi.org/10.1101/2022.05.16.492158

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