EBioMedicine (Mar 2022)

Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2

  • Nell Saunders,
  • Delphine Planas,
  • William H. Bolland,
  • Christophe Rodriguez,
  • Slim Fourati,
  • Julian Buchrieser,
  • Cyril Planchais,
  • Matthieu Prot,
  • Isabelle Staropoli,
  • Florence Guivel-Benhassine,
  • Françoise Porrot,
  • David Veyer,
  • Hélène Péré,
  • Nicolas Robillard,
  • Madelina Saliba,
  • Artem Baidaliuk,
  • Aymeric Seve,
  • Laurent Hocqueloux,
  • Thierry Prazuck,
  • Felix A. Rey,
  • Hugo Mouquet,
  • Etienne Simon-Lorière,
  • Timothée Bruel,
  • Jean-Michel Pawlotsky,
  • Olivier Schwartz

Journal volume & issue
Vol. 77
p. 103934

Abstract

Read online

Summary: Background: SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in the UK and had been detected in dozens of countries. It has since then been supplanted by Omicron. The AY.4.2 spike displays three additional mutations (T95I, Y145H and A222V) in the N-terminal domain when compared to the original Delta variant (B.1.617.2) and remains poorly characterized. Methods: We compared the Delta and the AY.4.2 spikes, by assessing their binding to antibodies and ACE2 and their fusogenicity. We studied the sensitivity of an authentic AY.4.2 viral isolate to neutralizing antibodies. Findings: The AY.4.2 spike exhibited similar binding to all the antibodies and sera tested, and similar fusogenicity and binding to ACE2 than the ancestral Delta spike. The AY.4.2 virus was slightly less sensitive than Delta to neutralization by a panel of monoclonal antibodies; noticeably, the anti-RBD Imdevimab showed incomplete neutralization. Sensitivity of AY.4.2 to sera from vaccinated individuals was reduced by 1.3 to 3-fold, when compared to Delta. Interpretation: Our results suggest that mutations in the NTD remotely impair the efficacy of anti-RBD antibodies. The spread of AY.4.2 was not due to major changes in spike fusogenicity or ACE2 binding, but more likely to a partially reduced neutralization sensitivity. Funding: The work was funded by Institut Pasteur, Fondation pour la Recherche Médicale, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute, Labex IBEID, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR.

Keywords