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

  • bioRxiv. 2024 Feb 9:2023.11.20.567873. doi: 10.1101/2023.11.20.567873.
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 Boland  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 ,  COVID-SER study group ,  Laurent Hocqueloux  12 ,  Thierry Prazuck  12 ,  Etienne Simon-Loriere  4  6 ,  Olivier Schwartz  1  2
Affiliations
  • 1. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France.
  • 2. Vaccine Research Institute, Créteil, France.
  • 3. Pathogenesis of Vascular Infections Unit, Institut Pasteur, INSERM, Paris, France.
  • 4. G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France.
  • 5. Bioinformatics and Biostatistics Hub, Paris, France.
  • 6. National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.
  • 7. Humoral Immunology Laboratory, Institut Pasteur, Université Paris Cité, INSERM U1222, Paris, France.
  • 8. Laboratoire de Virologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Paris, France.
  • 9. Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordeliers, INSERM, Université de Paris, Sorbonne Université, Paris, France.
  • 10. Laboratoire de Virologie, Institut des Agents Infectieux, Centre National de Référence des virus des infections respiratoires, Hospices Civils de Lyon, Lyon, France.
  • 11. CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, Lyon, France.
  • 12. CHU d'Orléans, Service de Maladies Infectieuses, Orléans, France.
PMID: 38045308 DOI: 10.1101/2023.11.20.567873
Abstract

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.

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