<p>Binding of monoclonal antibodies isolated from SARS-CoV-2 breakthrough infections to bat sarbecovirus RBDs.</p>

<p><b>(A)</b> Neutralisation of SARS-CoV-2 and Rs4231 RBD chimeras with SARS-CoV-2 RBD-specific monoclonal antibodies (mAb) (IC₅₀ µg/ml), with dotted lines linking matched samples. The <i>p</i> values are shown, calculated by comparing the change in mean IC₅₀ value and by using Tukey’s multiple comparison tests, respectively<b>. (B)</b> Spike structure of SARS-CoV-2 with 2 RBD-down and 1 RBD-up (PDB 7QTI) with the binding epitope regions of the different mAb competition groups is shown with both a side- and top-view (Group 1 = purple, Group 2 = orange, Group 3 = red, Group 3.5 = blue, Group 4 = green, Group 8 = non-RBD, NTD-specific, defined previously [<a href="plosbiology.org/article/info:doi/10.1371/journal.pbio.3003944#pbio.3003944.ref046" target="_blank">46</a>–<a href="plosbiology.org/article/info:doi/10.1371/journal.pbio.3003944#pbio.3003944.ref048" target="_blank">48</a>]. <b>(C)</b> SARS-CoV-2 RBD structures (PDB 7QTI) highlighting a broad epitope footprint of the mAb competition groups corresponding binding data.

Each of the plots shows a single mAb binding in an ELISA using purified <b>(C)</b> SARS-CoV-2 or <b>(E)</b> other bat sarbecovirus RBDs. Plots show raw optical density (OD) values with curves calculated using a least-squares regression non-linear fit. <b>(D)</b> Epitope binning by surface plasmon resonance (SPR) identifies 5 epitope communities broadly aligning with the antibody competition groups. Grey circles indicate communities by setting the associated dendrogram threshold to 0.45.