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

Elko, E. A.; Mead, H.; Nelson, G. A.; Zaia, J.; Ladner, J. T.; Altin, J. A.

doi:10.1101/2023.08.22.554362

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bioRxiv · 10.1101/2023.08.22.554362

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

Elko, E. A.·Mead, H.·Nelson, G. A.·Zaia, J.·Ladner, J. T.·Altin, J. A.

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Abstract

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.

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Elko, E. A., Mead, H., Nelson, G. A., Zaia, J., Ladner, J. T., Altin, J. A.. 2023-08-23. Recurrent SARS-CoV-2 mutations at Spike D796 evade antibodies from pre-Omicron convalescent and vaccinated subjects. https://doi.org/10.1101/2023.08.22.554362

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