A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..

A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.

Errataetall:

UpdateOf: bioRxiv. 2022 Oct 13;:. - PMID 36263061

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:186

Enthalten in:

Cell - 186(2023), 6 vom: 16. März, Seite 1263-1278.e20

Sprache:

Englisch

Beteiligte Personen:

Dadonaite, Bernadeta [VerfasserIn]
Crawford, Katharine H D [VerfasserIn]
Radford, Caelan E [VerfasserIn]
Farrell, Ariana G [VerfasserIn]
Yu, Timothy C [VerfasserIn]
Hannon, William W [VerfasserIn]
Zhou, Panpan [VerfasserIn]
Andrabi, Raiees [VerfasserIn]
Burton, Dennis R [VerfasserIn]
Liu, Lihong [VerfasserIn]
Ho, David D [VerfasserIn]
Chu, Helen Y [VerfasserIn]
Neher, Richard A [VerfasserIn]
Bloom, Jesse D [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Neutralizing
Antibodies, Viral
Antibody escape
Antibody neutralization
BA.1
Deep mutational scanning
Delta
Journal Article
Omicron
Pseudovirus
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
SARS-CoV-2
Spike

Anmerkungen:

Date Completed 21.03.2023

Date Revised 06.11.2023

published: Print-Electronic

UpdateOf: bioRxiv. 2022 Oct 13;:. - PMID 36263061

Citation Status MEDLINE

doi:

10.1016/j.cell.2023.02.001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353741116