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

• Published in: Microbiology spectrum Vol. 12; no. 2; p. e0329123
• Main Authors: Elko, Evan A., Mead, Heather L., Nelson, Georgia A., Zaia, John A., Ladner, Jason T., Altin, John A.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 06.02.2024
• 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; coronavirus; immune evasion; assay development; viral immunity; vaccination
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.03291-23

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. Severe 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.