Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2
Preprint
- 10 January 2022
- preprint
- research article
- Published by Cold Spring Harbor Laboratory
Abstract
SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in UK and has been detected in dozens of countries. It has since then been supplanted by the Omicron variant. AY.4.2 displays three additional mutations (T95I, Y145H and A222V) in the N-terminal domain (NTD) of the spike when compared to the original Delta variant (B.1.617.2) and remains poorly characterized. Here, we analyzed the fusogenicity of the AY.4.2 spike and the sensitivity of an authentic AY.4.2 isolate to neutralizing antibodies. The AY.4.2 spike exhibited similar fusogenicity and binding to ACE2 than Delta. The sensitivity of infectious AY.4.2 to a panel of monoclonal neutralizing antibodies was similar to Delta, except for the anti-RBD Imdevimab, which showed incomplete neutralization. Sensitivity of AY.4.2 to sera from individuals having received two or three doses of Pfizer or two doses of AstraZeneca vaccines was reduced by 1.7 to 2.1 fold, when compared to Delta. Our results suggest that mutations in the NTD remotely impair the efficacy of anti-RBD antibodies. The temporary spread of AY.4.2 was not associated with major changes in spike function but rather to a partially reduced neutralization sensitivity.Keywords
Other Versions
- Published version: Version EBioMedicine, 77, preprints
This publication has 41 references indexed in Scilit:
- Prospective mapping of viral mutations that escape antibodies used to treat COVID-19Science, 2021
- IgA dominates the early neutralizing antibody response to SARS-CoV-2Science Translational Medicine, 2021
- Syncytia formation by SARS‐CoV‐2‐infected cellsThe EMBO Journal, 2020
- SARS-CoV-2 neutralizing antibody structures inform therapeutic strategiesNature, 2020
- A comparison of four serological assays for detecting anti–SARS-CoV-2 antibodies in human serum samples from different populationsScience Translational Medicine, 2020
- Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spikeNature, 2020
- Cryo-EM structure of the 2019-nCoV spike in the prefusion conformationScience, 2020
- GISAID: Global initiative on sharing all influenza data – from vision to realityEurosurveillance, 2017
- Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal AntibodiesPLoS Pathogens, 2015
- Efficient generation of human IgA monoclonal antibodiesJournal of Immunological Methods, 2015