Cryptic-site-specific antibodies to the SARS-CoV-2 receptor binding domain can retain functional binding affinity to spike variants.
Kan LiRichard H C HuntworkGillian Q HornMilite AbrahaKathryn M HastieHaoyang LiVamseedhar RayaproluEduardo OlmedillasElizabeth FeeneyKenneth CroninSharon L SchendelMark HeiseDaniel BedingerMelissa D MattocksRalph S BaricS Munir AlamErica Ollmann SaphireGeorgia D TomarasS Moses DennisonPublished in: Journal of virology (2023)
Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is therefore important to further understand how antibody binding and neutralization are affected by the mutations in SARS-CoV-2 variants. We highlighted how antibody epitope specificity can influence antibody binding to SARS-CoV-2 spike protein variants and neutralization of SARS-CoV-2 variants. We showed that weakened spike binding and neutralization of Beta (B.1.351) and Omicron (BA.1) variants compared to wildtype are not universal among the panel of antibodies and identified antibodies of a specific binding footprint exhibiting consistent enhancement of spike binding and retained neutralization to Beta variant. These data and analysis can inform how antigen-targeting by antibodies might evolve during a pandemic and prepare for potential future sarbecovirus outbreaks.