Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail DOI Creative Commons
Amin Addetia, Young‐Jun Park, Tyler N. Starr

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112621 - 112621

Published: May 26, 2023

Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated the REGEN-COV therapeutic monoclonal (mAb) COVID-19 cocktail AZD1061 (COV2-2130) mAb. Here, we show that this remodels site allosterically, thereby altering epitopes recognized these three mAbs vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate spectacular structural functional plasticity RBD, which continuously evolving in emerging variants, including currently circulating strains are accumulating mutations antigenic sites remodeled substitution.

Language: Английский

Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution DOI Creative Commons
Tyler N. Starr, Allison J. Greaney, William W. Hannon

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6604), P. 420 - 424

Published: June 28, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved variants with substitutions in the spike receptor-binding domain (RBD) that affect its affinity for angiotensin-converting enzyme (ACE2) receptor and recognition by antibodies. These could also shape future evolution modulating effects of mutations at other sites-a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure on ACE2 binding all single-amino acid Wuhan-Hu-1, Alpha, Beta, Delta, Eta variant RBDs. Some substitutions, most prominently Asn

Language: Английский

Citations

248
Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models DOI
Alexander A. Cohen, Neeltje van Doremalen, Allison J. Greaney

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6606)

Published: July 5, 2022

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes are conserved relatively occluded rather than variable, immunodominant, exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 seven animal sarbecoviruses) homotypic (only SARS-CoV-2) RBD in mice macaques observed stronger mismatched (not on nanoparticles) strains, including SARS-CoV sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization SARS-CoV-2 variants, Omicrons, protected from challenges, whereas only challenge. Epitope mapping demonstrated increased targeting after immunization. Together, these results suggest could protect spillovers.

Language: Английский

Citations

199
SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape DOI Creative Commons
Sandile Cele, Farina Karim, Gila Lustig

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(2), P. 154 - 162.e5

Published: Jan. 13, 2022

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization a strain evolved over 6 months ancestral virus person with advanced HIV disease South Africa; this was infected prior to emergence Beta and Delta variants. longitudinally tracked tested it against self-plasma convalescent plasma ancestral, Beta, infections. Early similar but multitude mutations found Omicron other It showed substantial incomplete Pfizer BNT162b2 escape, weak by self-plasma, despite pre-dating Delta, also extensive escape infection-elicited neutralization. This example is consistent notion evolving individual immune-compromised hosts, including those disease, gain immune vaccines enhanced immunity, has implications for vaccine breakthrough reinfections.

Language: Английский

Citations

196
Antibody tests for identification of current and past infection with SARS-CoV-2 DOI
Tilly Fox, Julia Geppert, Jacqueline Dinnes

et al.

Cochrane library, Journal Year: 2022, Volume and Issue: 2022(11)

Published: Nov. 17, 2022

Language: Английский

Citations

178
Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains DOI Creative Commons
Tyler N. Starr, Allison J. Greaney, Cameron Stewart

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(11), P. e1010951 - e1010951

Published: Nov. 18, 2022

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes impacts of on these biochemical properties, enabling rapid assessment new seen during viral surveillance. However, effects can change as virus evolves, requiring updated deep scans. We determined all single amino acid Omicron BA.1 BA.2 RBDs ACE2-binding affinity, RBD folding, escape from binding by LY-CoV1404 (bebtelovimab) monoclonal antibody. The some differ those measured ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble previously Alpha variant due convergent epistatically modifying N501Y substitution. variants show additional lineage-specific shifts, including examples phenomenon entrenchment causes Q498R substitutions present be more favorable background than earlier strains. In contrast, substitution Q493R exhibits no sign entrenchment, with derived state, R493, being unfavorable for Wuhan-Hu-1. Likely this reason, R493Q reversion has occurred sub-variants BA.4/BA.5 BA.2.75, where affinity buffer may potentiate concurrent antigenic change. Consistent prior studies, we find have reduced expression, identify candidate stabilizing ameliorate deficit. Last, our maps highlight a broadening sites compared datasets landscape inform ongoing efforts

Language: Английский

Citations

167
An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain DOI Creative Commons
Allison J. Greaney, Tyler N. Starr, Jesse D. Bloom

et al.

Virus Evolution, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 1, 2022

Abstract A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited vaccination or infection. Unfortunately, direct experimental characterization new lags their sequence-based identification. Here we help address this challenge aggregating deep mutational scanning data into an ‘escape estimator’ estimates the antigenic effects arbitrary combinations virus’s spike receptor-binding domain. The estimator can be used intuitively visualize how impact antibody recognition and score expected effect mutations. These scores correlate assays performed on SARS-CoV-2 emphasize ominous properties recently described Omicron variant. An interactive version at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/ (last accessed 11 March 2022), provide a Python module for batch processing. Currently calculator uses primarily Wuhan-Hu-1-like infection so work best calculating escape from such immunity relative early strains.

Language: Английский

Citations

130
Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection DOI Open Access
Ali Zhang, Hannah D. Stacey, Michael R. D’Agostino

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 381 - 396

Published: Dec. 19, 2022

Language: Английский

Citations

130
Molecular fate-mapping of serum antibody responses to repeat immunization DOI Open Access
Ariën Schiepers,

Marije F. L. van ’t Wout,

Allison J. Greaney

et al.

Nature, Journal Year: 2023, Volume and Issue: 615(7952), P. 482 - 489

Published: Jan. 16, 2023

Language: Английский

Citations

117
Mapping SARS-CoV-2 antigenic relationships and serological responses DOI Creative Commons
Samuel Wilks, Barbara Mühlemann, Xiaoying Shen

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6666)

Published: Oct. 6, 2023

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns cross-reactivity among 21 and 15 groups human sera obtained after primary infection with 10 different or messenger RNA (mRNA)–1273 mRNA-1273.351 vaccination. We found differences pre-Omicron caused by substitutions at spike-protein positions 417, 452, 484, 501. Quantifying changes in response breadth over time additional vaccine doses, our results show largest increase between 4 weeks >3 months a second dose. immunodominance spike regions, depending on variant an individual was first to, implications for risk assessment vaccine-strain selection.

Language: Английский

Citations

100
Coronavirus Resistance Database (CoV-RDB): SARS-CoV-2 susceptibility to monoclonal antibodies, convalescent plasma, and plasma from vaccinated persons DOI Creative Commons
Philip L. Tzou, Kaiming Tao, Sergei L. Kosakovsky Pond

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(3), P. e0261045 - e0261045

Published: March 9, 2022

As novel SARS-CoV-2 variants with different patterns of spike protein mutations have emerged, the susceptibility these to neutralization by antibodies has been rapidly assessed. However, data are generated using approaches and scattered across publications making it difficult for be located synthesized. The Stanford Coronavirus Resistance Database (CoV-RDB; https://covdb.stanford.edu ) is designed house comprehensively curated published on neutralizing monoclonal (mAbs), convalescent plasma (CP), vaccinee (VP). December 31, 2021, CoV-RDB encompassed 257 including 91 (35%) containing 9,070 mAb results, 131 (51%) 16,773 CP 178 (69%) 33,540 VP results. database also records which selected during in vitro passage presence mAbs emerge persons receiving as treatment. interface interactively displays at levels granularity filtering and/or aggregating query results according one or more experimental conditions. website provides a companion sequence analysis program that outputs information about present submitted assists users determining appropriate mutation-detection thresholds identifying non-consensus amino acids. most recent underlying can downloaded its entirety from GitHub repository documented machine-readable format.

Language: Английский

Citations

95