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An Antigenic Space Framework for Understanding Antibody Escape of SARS-CoV-2 Variants.
Miller, Nathaniel L; Clark, Thomas; Raman, Rahul; Sasisekharan, Ram.
  • Miller NL; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Clark T; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Raman R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Sasisekharan R; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Viruses ; 13(10)2021 10 06.
Article in English | MEDLINE | ID: covidwho-1463832
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Binding Sites, Antibody / Antibodies, Neutralizing / Immune Evasion / SARS-CoV-2 / Antibodies, Viral Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13102009

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Binding Sites, Antibody / Antibodies, Neutralizing / Immune Evasion / SARS-CoV-2 / Antibodies, Viral Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13102009