Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes

William N. Voss, Yixuan J. Hou, Nicole V. Johnson, George Delidakis, Jin Eyun Kim, Kamyab Javanmardi, Andrew P. Horton, Foteini Bartzoka, Chelsea J. Paresi, Yuri Tanno, Chia Wei Chou, Shawn A. Abbasi, Whitney Pickens, Katia George, Daniel R. Boutz, Dalton M. Towers, Jonathan R. McDaniel, Daniel Billick, Jule Goike, Lori RoweDhwani Batra, Jan Pohl, Justin Lee, Shivaprakash Gangappa, Suryaprakash Sambhara, Michelle Gadush, Nianshuang Wang, Maria D. Person, Brent L. Iverson, Jimmy D. Gollihar, John M. Dye, Andrew S. Herbert, Ilya J. Finkelstein, Ralph S. Baric, Jason S. McLellan, George Georgiou, Jason J. Lavinder, Gregory C. Ippolito

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an amino (N)-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multidonor class of “public” antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that “public” NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.

Original languageEnglish (US)
Pages (from-to)1108-1112
Number of pages5
Issue number6546
StatePublished - Jun 4 2021


  • Animals
  • Antibodies, Monoclonal/blood
  • Antibodies, Neutralizing/blood
  • Antibodies, Viral/blood
  • Antibody Affinity
  • COVID-19/immunology
  • Epitopes/immunology
  • Humans
  • Immune Evasion
  • Immunoglobulin G/blood
  • Immunoglobulin Heavy Chains/immunology
  • Immunoglobulin Variable Region/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Protein Domains
  • Proteomics
  • SARS-CoV-2/genetics
  • Spike Glycoprotein, Coronavirus/chemistry

ASJC Scopus subject areas

  • General


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