SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency
Copyright © 2023 Elsevier Inc. All rights reserved..
BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:187 |
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| Enthalten in: |
Cell - 187(2024), 3 vom: 01. Feb., Seite 596-608.e17 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Lu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.02.2024 Date Revised 06.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2023.12.025 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency |
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| 500 | |a Date Revised 06.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BA.2.86 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Spike protein | |
| 650 | 4 | |a TMPRSS2 | |
| 650 | 4 | |a antibody evasion | |
| 650 | 4 | |a fusion | |
| 650 | 4 | |a infectivity | |
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| 650 | 4 | |a mutations | |
| 650 | 4 | |a pirola variant | |
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| 650 | 7 | |a Antibodies, Viral |2 NLM | |
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| 700 | 1 | |a Kempf, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Nehlmeier, Inga |e verfasserin |4 aut | |
| 700 | 1 | |a Cossmann, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Richter, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Bdeir, Najat |e verfasserin |4 aut | |
| 700 | 1 | |a Graichen, Luise |e verfasserin |4 aut | |
| 700 | 1 | |a Moldenhauer, Anna-Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Dopfer-Jablonka, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Stankov, Metodi V |e verfasserin |4 aut | |
| 700 | 1 | |a Simon-Loriere, Etienne |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Sebastian R |e verfasserin |4 aut | |
| 700 | 1 | |a Jäck, Hans-Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Čičin-Šain, Luka |e verfasserin |4 aut | |
| 700 | 1 | |a Behrens, Georg M N |e verfasserin |4 aut | |
| 700 | 1 | |a Drosten, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Pöhlmann, Stefan |e verfasserin |4 aut | |
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