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

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• Alternative Title:
  Science
• Personal Author:
  Voss, William N. ; Hou, Yixuan J. ; Johnson, Nicole V. ; Delidakis, George ; Kim, Jin Eyun ; Javanmardi, Kamyab ; Horton, Andrew P. ; Bartzoka, Foteini ; Paresi, Chelsea J. ; Tanno, Yuri ; Chou, Chia-Wei ; Abbasi, Shawn A. ; Pickens, Whitney ; George, Katia ; Boutz, Daniel R. ; Towers, Dalton M. ; McDaniel, Jonathan R. ; Billick, Daniel ; Goike, Jule ; Rowe, Lori ; Batra, Dhwani ; Pohl, Jan ; Lee, Justin ; Gangappa, Shivaprakash ; Sambhara, Suryaprakash ; Gadush, Michelle ; Wang, Nianshuang ; Person, Maria D. ; Iverson, Brent L. ; Gollihar, Jimmy D. ; Dye, John ; Herbert, Andrew ; Finkelstein, Ilya J. ; Baric, Ralph S. ; McLellan, Jason S. ; Georgiou, George ; Lavinder, Jason J. ; Ippolito, Gregory C.
• Description:
  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.
• Subjects:
  Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Antibody Affinity Coronavirus Infections COVID-19 Epitopes Humans Immune Evasion Immunoglobulin G Immunoglobulin Heavy Chains Immunoglobulin Variable Region Mice Mice, Inbred BALB C Mutation Protein Domains Proteomics SARS-CoV-2 Spike Glycoprotein, Coronavirus

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• Source:
  Science. 2021;
• Pubmed ID:
  33947773
• Pubmed Central ID:
  PMC8224265
• Document Type:
  Journal Article
• Funding:
  75N93019C00050/AI/NIAID NIH HHSUnited States/ ; P41 GM103311/GM/NIGMS NIH HHSUnited States/ ; R01 AI127521/AI/NIAID NIH HHSUnited States/ ; U54 CA260543/CA/NCI NIH HHSUnited States/
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:3dd4c5ed7481b219c1f62ea170fe7a1b3d6123000e229e4ee806071f2ae4c458
• Download URL:
  https://stacks.cdc.gov/view/cdc/107914/cdc_107914_DS1.pdf
• File Type:
  [PDF - 2.85 MB ]