An Antigenic Space Framework for Understanding Antibody Escape of SARS-CoV-2 Variants
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viruses-13-02009.pdf
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2.36 MB
Format
Adobe PDF
Checksum (MD5)
16420adb13f38ea32c61d7f0381ce4f0
Author(s)
Miller, Nathaniel L.
Clark, Thomas
Raman, Rahul
Sasisekharan, Ram
Date Issued
October 2021
Journal
Viruses
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Miller, Nathaniel L. et al. "An Antigenic Space Framework for Understanding Antibody Escape of SARS-CoV-2 Variants." Viruses 13, 10 (October 2021): 2009. © 2021 by the authors
Version
Final published version
Abstract
The evolution of mutations in SARS-CoV-2 at antigenic sites that impact neutralizing antibody responses in humans poses a risk to immunity developed through vaccination and natural infection. The highly successful RNA-based vaccines have enabled rapid vaccine updates that incorporate mutations from current variants of concern (VOCs). It is therefore important to anticipate future antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this goal, we survey epitope-paratope interfaces of anti-SARS-CoV-2 antibodies to map an antigenic space that captures the role of each spike protein residue within the polyclonal antibody response directed against the ACE2-receptor binding domain (RBD) or the N-terminal domain (NTD). In particular, the antigenic space map builds on recently published epitope definitions by annotating epitope overlap and orthogonality at the residue level. We employ the antigenic space map as a framework to understand how mutations on nine major variants contribute to each variant’s evasion of neutralizing antibodies. Further, we identify constellations of mutations that span the orthogonal epitope regions of the RBD and NTD on the variants with the greatest antibody escape. Finally, we apply the antigenic space map to predict which regions of antigenic space—should they mutate—may be most likely to complementarily augment antibody evasion for the most evasive and transmissible VOCs.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Harvard University--MIT Division of Health Sciences and Technology
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Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3390/v13102009
