An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain
Open accessPublished version of a preprint
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 by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/ (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.
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Deep mutational scanning experiments of the SARS-CoV-2 receptor binding domain suggest that further mutations of Omicron BA.1/2 at sites 452 and 486 could lead to further immune evasion against antibodies isolated from individuals who had pre-Omicron and Omicron BA.1 breakthrough infections.
“Deep mutational scanning experiments of the SARS-CoV-2 receptor binding domain suggest that further mutations of Omicron BA.1/2 at sites 452 and 486 could lead to further immune evasion against antibodies isolated from individuals who had pre-Omicron and Omicron BA.1 breakthrough infections 21,28,29 .”
From Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (2023) · cites this paper as [29]
Deep mutational scanning suggests that F486 is a key site for escape of vaccine-elicited and infection-elicited RBD-targeted antibodies, including those still able to neutralize Omicron/BA.1.
“Deep mutational scanning suggests that F486 is a key site for escape of vaccine-elicited and infection-elicited RBD-targeted antibodies, including those still able to neutralize Omicron/BA.1 (https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/)14.”
From Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa (2022) · cites this paper as [14]
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References 28 · Cited by 147
- Authors
- Greaney, A. J., Starr, T. N., & Bloom, J. D.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bloom, Jesse D
- Venue
- Virus Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-01-01
- Volume
- 8
- Issue
- 1
- Pages
- veac021-veac021
- ISSN
- 2057-1577 (ISSN-L)
- PMC
- PMC9092643
- OpenAlex
- W4226443473
- Cited by
- 147
- References
- 28
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 25 · 2023: 41 · 2022: 36 · 2021: 3
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Virus Evolution (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- Funders
- National Institutes of Health/National Institute of Allergy and Infectious Diseases (HHS75N93021C00015 R01AI141707 (to J.D.B.) and T32AI083203)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- SARS-CoV-2, spike protein receptor-binding domain, antibody escape, deep mutational scanning, neutralizing antibodies, Omicron variant, viral variants, vaccine-induced immunity
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