Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion
Delphine Planas, Isabelle Staropoli, Vincent Michel, Frédéric Lemoine, Flora Donati, Matthieu Prot, Françoise Porrot, Florence Guivel‐Benhassine, Banujaa Jeyarajah, Angela Brisebarre, Océane Dehan, Léa Avon, William Bolland, Mathieu Hubert, Julian Buchrieser, Thibault Vanhoucke, Pierre Rosenbaum, David Veyer, Hélène Péré, Bruno Lina, Sophie Trouillet‐Assant, Laurent Hocqueloux, Thiérry Prazuck, Etienne Simon‐Lorière, Olivier Schwartz
Abstract
The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize 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 replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays 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.