Recurrent SARS-CoV-2 mutations at Spike D796 evade antibodies from pre-Omicron convalescent and vaccinated subjects

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the receptor-binding domai...

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Bibliographic Details
Published in:Microbiology spectrum 2024-02, Vol.12 (2), p.e0329123-e0329123
Main Authors: Elko, Evan A, Mead, Heather L, Nelson, Georgia A, Zaia, John A, Ladner, Jason T, Altin, John A
Format: Article
Language:English
Subjects:
Antibodies, Neutralizing
Antibodies, Viral
assay development
coronavirus
COVID-19
Humans
immune evasion
Immunology
Mutation
Research Article
SARS-CoV-2
Spike Glycoprotein, Coronavirus
vaccination
viral immunity
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Summary:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the receptor-binding domain, Omicron features amino acid mutations elsewhere in the Spike protein; however, their effects generally remain ill defined. The Spike D796Y substitution is present in all Omicron sub-variants and occurs at the same site as a mutation (D796H) selected during viral evolution in a chronically infected patient. Here, we map antibody reactivity to a linear epitope in the Spike protein overlapping position 796. We show that antibodies binding this region arise in pre-Omicron SARS-CoV-2 convalescent and vaccinated subjects but that both D796Y and D796H abrogate their binding. These results suggest that D796Y contributes to the fitness of Omicron in hosts with pre-existing immunity to other variants of SARS-CoV-2 by evading antibodies targeting this site.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved substantially through the coronavirus disease 2019 (COVID-19) pandemic: understanding the drivers and consequences of this evolution is essential for projecting the course of the pandemic and developing new countermeasures. Here, we study the immunological effects of a particular mutation present in the Spike protein of all Omicron strains and find that it prevents the efficient binding of a class of antibodies raised by pre-Omicron vaccination and infection. These findings reveal a novel consequence of a poorly understood Omicron mutation and shed light on the drivers and effects of SARS-CoV-2 evolution.
ISSN:2165-0497
2165-0497
DOI:10.1128/spectrum.03291-23