Journal
MOLECULAR CELL
Volume 81, Issue 24, Pages 5099-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2021.11.024
Keywords
-
Categories
Funding
- Welch Foundation [F-1808, F-1390]
- Bill and Melinda Gates Foundation [INV-017592]
- UT Austin [W911NF-17-2-0091]
- ARL [W911NF-17-2-0091]
- Bill and Melinda Gates Foundation [INV-017592] Funding Source: Bill and Melinda Gates Foundation
Ask authors/readers for more resources
The Spike Display platform characterized 200 variant SARS-CoV-2 spikes, revealing a public epitope in the N-terminal domain loops that is recognized by most NTD-binding nAbs. Mutations in NTDs of variants like B.1.1.7, B.1.351, B.1.1.28, B.1.427/B.1.429, and B.1.617.2 impact spike expression and escape most NTD-targeting nAbs. Certain variants like B.1.351 and B.1.1.28 completely evade binding by a potent ACE2 mimic.
The SARS-CoV-2 spike protein is a critical component of vaccines and a target for neutralizing monoclonal antibodies (nAbs). Spike is also undergoing immunogenic selection with variants that increase infectivity and partially escape convalescent plasma. Here, we describe Spike Display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed-200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by 13 nAbs. An alanine scan of all five N-terminal domain (NTD) loops highlights a public epitope in the N1, N3, and N5 loops recognized by most NTD-binding nAbs. NTD mutations in variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.1.28 (gamma), B.1.427/B.1.429 (epsilon), and B.1.617.2 (delta) impact spike expression and escape most NTD-targeting nAbs. Finally, B.1.351 and B.1.1.28 completely escape a potent ACE2 mimic. We anticipate that Spike Display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available