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

Delphine Planas (1, 2) , Isabelle Staropoli (1) , Vincent Michel (3) , Frederic Lemoine (4, 5) , Flora Donati (4, 6) , Matthieu Prot (4) , Francoise Porrot (1) , Florence Guivel-Benhassine (1) , Banujaa Jeyarajah (6) , Angela Brisebarre (6) , Océane Dehan (6) , Léa Avon (6) , William Henry Bolland (1) , Mathieu Hubert (1) , Julian Buchrieser (1) , Thibault Vanhoucke (1) , Pierre Rosenbaum (7) , David Veyer (8, 9) , Hélène Péré (8, 9) , Bruno Lina (10, 11) , Sophie Trouillet-Assant (10, 11) , Laurent Hocqueloux (12) , Thierry Prazuck (12) , Etienne Simon-Loriere (4, 6) , Olivier Schwartz (1, 2)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 VRI - Vaccine Research Institute [Créteil, France]
3 Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections
4 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
5 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
6 CNR - laboratoire associé - Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Paris]
7 Immunologie humorale - Humoral Immunology
8 Service de Microbiologie [CHU GeorgesPompidou]
9 FunGeST - Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC]
10 CNR - laboratoire coordonnateur - Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Lyon]
11 CIRI - Centre International de Recherche en Infectiologie
12 CHRO - Centre Hospitalier Régional d'Orléans

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.

Domains: Life Sciences [q-bio]

Delphine Planas, Isabelle Staropoli, Vincent Michel, Frederic Lemoine, Flora Donati, et al.. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion. Nature Communications, 2024, 15 (1), pp.2254. ⟨10.1038/s41467-024-46490-7⟩. ⟨pasteur-04530809⟩