Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants
Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants
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.
Lozanski Gerard、Zou Xue、Oltz Eugene M.、Evans John P.、Zheng Yi-Min、Carlin Claire、Bednash Joseph S.、Qu Panke、Faraone Julia N.、Liu Shan-Lu、Saif Linda J.、Mallampalli Rama K.、Mohler Peter J.、Gumina Richard J.
Department of Pathology, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State UniversityDepartment of Microbial Infection and Immunity, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State University||Molecular, Cellular, and Developmental Biology Program, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State UniversityDepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State UniversityDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State University||Molecular, Cellular, and Developmental Biology Program, The Ohio State UniversityCenter for Retrovirus Research, The Ohio State University||Department of Veterinary Biosciences, The Ohio State University||Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University||Department of Microbial Infection and Immunity, The Ohio State UniversityCenter for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, The Ohio State University||Veterinary Preventive Medicine Department, College of Veterinary Medicine, The Ohio State University||Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State UniversityDepartment of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State UniversityDepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University||Frick Center for Heart Failure and Arrhythmia Research, The Ohio State University Wexner Medical Center||Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center||Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical CenterDepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University||Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center||Department of Physiology and Cell Biology, College of Medicine, The Ohio State University Wexner Medical Center
基础医学微生物学分子生物学
SARS-CoV-2OmicronCOVID-19BA.4BA.5BA.2.12.1mRNA vaccineneutralizing antibodyspike processingsyncytia formation
Lozanski Gerard,Zou Xue,Oltz Eugene M.,Evans John P.,Zheng Yi-Min,Carlin Claire,Bednash Joseph S.,Qu Panke,Faraone Julia N.,Liu Shan-Lu,Saif Linda J.,Mallampalli Rama K.,Mohler Peter J.,Gumina Richard J..Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants[EB/OL].(2025-03-28)[2025-04-24].https://www.biorxiv.org/content/10.1101/2022.05.16.492158.点此复制
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