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. 2021 Feb 22;12:1221. doi: 10.1038/s41467-021-21463-2

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Antigenic regions/sites within the spike protein recognized by plasma antibodies following SARS-CoV-2 infection (based on data presented in Fig. 3). The amino acid designation is based on the spike protein sequence encoded by the SARS-CoV-2 Wuhan-Hu-1 strain (GenBank: MN908947.3) spike. The antigenic regions/sites discovered using the post-infection antibodies are depicted below the SARS-CoV-2 spike schematic. The epitopes of each protein are numbered in a sequential fashion indicated in black. Antigenic sites shown in green letters (SARS CoV-2 S6 and S9.3) were uniquely recognized by post-SARS-CoV-2 infection IgG (a) or IgA (b) antibodies only in the “survived” but not from expired COVID-19 patients (as shown in Fig. 3). c, d Structural representation of S6 (c) and S9.3 (d) antigenic sites depicted in green on the surface of a monomer in a trimeric spike (PDB#6VSB) with a single receptor-binding domain (RBD) in the up conformation, wherever available using UCSF Chimera software version 1.11.2. The RBD region is shaded in red (residues 319–541) on both structures. e, f Seroreactivity of COVID-19 plasma samples with the selected synthetic peptides covering epitope S6 (receptor-binding motif; RBM) and peptide S9.3 (fusion peptide; FP). Absorbance at 100-fold dilution of early first sample (E) or last (L) sample from SARS-CoV-2 infected individuals were tested for binding to RBM (panel e) and FP (panel f) in IgG ELISA. The statistical significances between “expired” patients (red; n = 8 biologically independent individuals), “ICU-survived” patients (blue; n = 11 biologically independent individuals), and “non-ICU survived” patient (green; n = 6 biologically independent individuals) groups were determined by non-parametric (Kruskal–Wallis) statistical test using Dunn’s multiple comparisons analysis in GraphPad prism. p-values <0.05 were considered significant with a 95% confidence interval.