SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency

Zhang L, Kempf A, Nehlmeier I, Cossmann A, Richter A, Bdeir N, Graichen L, Moldenhauer AS, Dopfer-Jablonka A, Stankov MV, Simon-Loriere E, Schulz S, Jäck HM, Čičin-Šain L, Behrens GM, Drosten C, Hoffmann M, Pöhlmann S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cell Elsevier

Book Volume: 187

Pages Range: 596-608.e17

Journal Issue: 3

DOI: 10.1016/j.cell.2023.12.025

Abstract

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.

Authors with CRIS profile

Sebastian Schulz Professur für Immunologie Hans-Martin Jäck Department of Molecular Immunology

Additional Organisation(s)

FAU Profilzentrum Licht.Materie.Quantentechnologien (FAU LMQ)

Involved external institutions

Deutsches Primatenzentrum (DPZ), Leibniz-Institut für Primatenforschung DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Université Sorbonne Paris Cité FR France (FR)

How to cite

APA:

Zhang, L., Kempf, A., Nehlmeier, I., Cossmann, A., Richter, A., Bdeir, N.,... Pöhlmann, S. (2024). SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency. Cell, 187(3), 596-608.e17. https://dx.doi.org/10.1016/j.cell.2023.12.025

MLA:

Zhang, Lu, et al. "SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency." Cell 187.3 (2024): 596-608.e17.

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