Abstract
SummaryThe 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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic, causing > 200 million infections and > 4.3 million deaths worldwide
SARS-CoV-2 spike interacts with angiotensin-converting enzyme 2 (ACE2) and other cell surface receptors to mediate fusion between the virus envelope and cell membrane (Cantuti-Castelvetri et al, 2020; Yan et al, 2020; Zhang et al, 2020)
The S1 subunit, which is composed of the N-terminal domain (NTD) and receptor-binding domain (RBD) (Wrapp et al, 2020), is the key determinant of tissue and host tropism (Li, 2016)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic, causing > 200 million infections and > 4.3 million deaths worldwide (as of August 14, 2021). SARS-CoV-2 spike interacts with angiotensin-converting enzyme 2 (ACE2) and other cell surface receptors to mediate fusion between the virus envelope and cell membrane (Cantuti-Castelvetri et al, 2020; Yan et al, 2020; Zhang et al, 2020). The S1 subunit, which is composed of the N-terminal domain (NTD) and receptor-binding domain (RBD) (Wrapp et al, 2020), is the key determinant of tissue and host tropism (Li, 2016)
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