Paper

Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

Mathieu, Hubert, Pere, Helene, Bruno, Lina, Benhassine, Florence Guivel, Planas, Delphine, Prazuck, Thierry, Vincent, Michel, Donati, Flora, Jeyarajah, Banujaa, Prot, Matthieu, Buchreiser, Julian, Schwartz, Olivier, Sophie Trouillet Assant, Thibault Vanhoucke, Brisebarre, Angela, Etienne Simon Loriere, Lemoine, Frederic, Hocqueloux, Laurent, Avon, Lea, Porrot, Francoise, Veyer, David, Staropoli, Isabelle, Bolland, William, Rosenbaum, Pierre, Dehan, Oceane

2024

Overview

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.Competing Interest StatementThe authors have declared no competing interest.Footnotes* We isolated and analyzed the properties of JN.1, a BA.2.86.1 sublineage carrying the L455S spike substitution, that rapidly expanded worldwide and. JN.1 displays noticeable differences relative to BA.2.86.1.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: ACE2 / Angiotensin-converting enzyme 2 / Antibodies / Antiviral agents / Cell culture / Epithelial cells / Fitness / Microbiology / Mutation / Severe acute respiratory syndrome coronavirus 2