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Cell
. 2024 Jan 5:S0092-8674(23)01399-5.
doi: 10.1016/j.cell.2023.12.025. Online ahead of print. SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency
Lu Zhang 1 , Amy Kempf 1 , Inga Nehlmeier 2 , Anne Cossmann 3 , Anja Richter 4 , Najat Bdeir 5 , Luise Graichen 1 , Anna-Sophie Moldenhauer 2 , Alexandra Dopfer-Jablonka 6 , Metodi V Stankov 3 , Etienne Simon-Loriere 7 , Sebastian R Schulz 8 , Hans-Martin Jäck 8 , Luka Čičin-Šain 9 , Georg M N Behrens 10 , Christian Drosten 4 , Markus Hoffmann 11 , Stefan Pöhlmann 12
Affiliations
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.
Keywords: BA.2.86; SARS-CoV-2; Spike protein; TMPRSS2; antibody evasion; fusion; infectivity; lung cell entry; mutations; pirola variant.
. 2024 Jan 5:S0092-8674(23)01399-5.
doi: 10.1016/j.cell.2023.12.025. Online ahead of print. SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency
Lu Zhang 1 , Amy Kempf 1 , Inga Nehlmeier 2 , Anne Cossmann 3 , Anja Richter 4 , Najat Bdeir 5 , Luise Graichen 1 , Anna-Sophie Moldenhauer 2 , Alexandra Dopfer-Jablonka 6 , Metodi V Stankov 3 , Etienne Simon-Loriere 7 , Sebastian R Schulz 8 , Hans-Martin Jäck 8 , Luka Čičin-Šain 9 , Georg M N Behrens 10 , Christian Drosten 4 , Markus Hoffmann 11 , Stefan Pöhlmann 12
Affiliations
- PMID: 38194966
- DOI: 10.1016/j.cell.2023.12.025
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.
Keywords: BA.2.86; SARS-CoV-2; Spike protein; TMPRSS2; antibody evasion; fusion; infectivity; lung cell entry; mutations; pirola variant.