Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising in circulation – EG.5.1 and XBB.2.3, for their neutralization a...

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Main Authors: Julia N. Faraone, Panke Qu, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Linda J. Saif, Eugene M. Oltz, Kai Xu, Daniel Jones, Richard J. Gumina, Shan-Lu Liu
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2270069
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author Julia N. Faraone
Panke Qu
Negin Goodarzi
Yi-Min Zheng
Claire Carlin
Linda J. Saif
Eugene M. Oltz
Kai Xu
Daniel Jones
Richard J. Gumina
Shan-Lu Liu
author_facet Julia N. Faraone
Panke Qu
Negin Goodarzi
Yi-Min Zheng
Claire Carlin
Linda J. Saif
Eugene M. Oltz
Kai Xu
Daniel Jones
Richard J. Gumina
Shan-Lu Liu
author_sort Julia N. Faraone
collection DOAJ
description Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising in circulation – EG.5.1 and XBB.2.3, for their neutralization and syncytia formation. We determined the neutralizing antibody titers in sera of individuals that received a bivalent mRNA vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to a much less extent, two new EG.5.1 and XBB.2.3 variants. In fact, the enhanced neutralization escape of EG.5.1 appeared to be driven by its key defining mutation XBB.1.5-F456L. Notably, infection by BA.4/5 or XBB.1.5 afforded little, if any, neutralization against EG.5.1, XBB.2.3 and previous XBB variants – especially in unvaccinated individuals, with average neutralizing antibody titers near the limit of detection. Additionally, we investigated the infectivity, fusion activity, and processing of variant spikes for EG.5.1 and XBB.2.3 in HEK293T-ACE2 and CaLu-3 cells but found no significant differences compared to earlier XBB variants. Overall, our findings highlight the continued immune evasion of new Omicron subvariants and, more importantly, the need to reformulate mRNA vaccines to include XBB spikes for better protection.
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spelling doaj-art-b692e73b9e114a7989eec498d6f2e3312025-08-20T03:29:38ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2270069Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3Julia N. Faraone0Panke Qu1Negin Goodarzi2Yi-Min Zheng3Claire Carlin4Linda J. Saif5Eugene M. Oltz6Kai Xu7Daniel Jones8Richard J. Gumina9Shan-Lu Liu10Center for Retrovirus Research, The Ohio State University, Columbus, OH, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH, USADepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USACenter for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH, USADepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH, USADepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH, USAImmune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising in circulation – EG.5.1 and XBB.2.3, for their neutralization and syncytia formation. We determined the neutralizing antibody titers in sera of individuals that received a bivalent mRNA vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to a much less extent, two new EG.5.1 and XBB.2.3 variants. In fact, the enhanced neutralization escape of EG.5.1 appeared to be driven by its key defining mutation XBB.1.5-F456L. Notably, infection by BA.4/5 or XBB.1.5 afforded little, if any, neutralization against EG.5.1, XBB.2.3 and previous XBB variants – especially in unvaccinated individuals, with average neutralizing antibody titers near the limit of detection. Additionally, we investigated the infectivity, fusion activity, and processing of variant spikes for EG.5.1 and XBB.2.3 in HEK293T-ACE2 and CaLu-3 cells but found no significant differences compared to earlier XBB variants. Overall, our findings highlight the continued immune evasion of new Omicron subvariants and, more importantly, the need to reformulate mRNA vaccines to include XBB spikes for better protection.https://www.tandfonline.com/doi/10.1080/22221751.2023.2270069SARS-CoV-2Spikeneutralizing antibodymRNA vaccinationCOVID-19XBB.2.3
spellingShingle Julia N. Faraone
Panke Qu
Negin Goodarzi
Yi-Min Zheng
Claire Carlin
Linda J. Saif
Eugene M. Oltz
Kai Xu
Daniel Jones
Richard J. Gumina
Shan-Lu Liu
Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
Emerging Microbes and Infections
SARS-CoV-2
Spike
neutralizing antibody
mRNA vaccination
COVID-19
XBB.2.3
title Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
title_full Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
title_fullStr Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
title_full_unstemmed Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
title_short Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3
title_sort immune evasion and membrane fusion of sars cov 2 xbb subvariants eg 5 1 and xbb 2 3
topic SARS-CoV-2
Spike
neutralizing antibody
mRNA vaccination
COVID-19
XBB.2.3
url https://www.tandfonline.com/doi/10.1080/22221751.2023.2270069
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