Tags

Type your tag names separated by a space and hit enter

Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation.
Immunity. 2020 07 14; 53(1):98-105.e5.I

Abstract

Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.

Links

Publisher Full Text
ncbi.nlm.nih.gov
linkinghub.elsevier.com
PMC Free PDF
Aggregator Full Text

Authors+Show Affiliations

Seydoux E
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Homad LJ
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
MacCamy AJ
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Parks KR
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; University of Washington, Department of Global Health, Seattle, WA, USA.
Hurlburt NK
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Jennewein MF
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Akins NR
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Stuart AB
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Wan YH
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Feng J
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Whaley RE
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Singh S
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
Boeckh M
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Cohen KW
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA.
McElrath MJ
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; University of Washington, Department of Global Health, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Englund JA
Department of Pediatrics, University of Washington and Seattle Children's Research, Seattle, WA, USA.
Chu HY
Department of Medicine, University of Washington, Seattle, WA, USA.
Pancera M
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA. Electronic address: mpancera@fredhutch.org.
McGuire AT
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; University of Washington, Department of Global Health, Seattle, WA, USA. Electronic address: amcguire@fredhutch.org.
Stamatatos L
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Disease Division, Seattle, WA, USA; University of Washington, Department of Global Health, Seattle, WA, USA. Electronic address: lstamata@fredhutch.org.

MeSH

Angiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralB-LymphocytesBetacoronavirusBinding SitesCOVID-19Coronavirus InfectionsEpitopes, B-LymphocyteHumansPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein BindingReceptors, VirusSARS-CoV-2Somatic Hypermutation, ImmunoglobulinSpike Glycoprotein, CoronavirusViral Vaccines

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

32561270

Citation

Seydoux, Emilie, et al. "Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies With Limited Somatic Mutation." Immunity, vol. 53, no. 1, 2020, pp. 98-105.e5.
Seydoux E, Homad LJ, MacCamy AJ, et al. Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity. 2020;53(1):98-105.e5.
Seydoux, E., Homad, L. J., MacCamy, A. J., Parks, K. R., Hurlburt, N. K., Jennewein, M. F., Akins, N. R., Stuart, A. B., Wan, Y. H., Feng, J., Whaley, R. E., Singh, S., Boeckh, M., Cohen, K. W., McElrath, M. J., Englund, J. A., Chu, H. Y., Pancera, M., McGuire, A. T., & Stamatatos, L. (2020). Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity, 53(1), 98-e5. https://doi.org/10.1016/j.immuni.2020.06.001
Seydoux E, et al. Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies With Limited Somatic Mutation. Immunity. 2020 07 14;53(1):98-105.e5. PubMed PMID: 32561270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. AU - Seydoux,Emilie, AU - Homad,Leah J, AU - MacCamy,Anna J, AU - Parks,K Rachael, AU - Hurlburt,Nicholas K, AU - Jennewein,Madeleine F, AU - Akins,Nicholas R, AU - Stuart,Andrew B, AU - Wan,Yu-Hsin, AU - Feng,Junli, AU - Whaley,Rachael E, AU - Singh,Suruchi, AU - Boeckh,Michael, AU - Cohen,Kristen W, AU - McElrath,M Juliana, AU - Englund,Janet A, AU - Chu,Helen Y, AU - Pancera,Marie, AU - McGuire,Andrew T, AU - Stamatatos,Leonidas, Y1 - 2020/06/08/ PY - 2020/05/12/received PY - 2020/05/25/revised PY - 2020/05/28/accepted PY - 2020/6/21/pubmed PY - 2020/7/24/medline PY - 2020/6/21/entrez KW - ACE2 KW - B cells KW - COVID-19 KW - MERS KW - SARS KW - SARS-CoV-2 KW - antibodies KW - neutralization KW - receptor-binding domain KW - spike protein SP - 98 EP - 105.e5 JF - Immunity JO - Immunity VL - 53 IS - 1 N2 - Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design. SN - 1097-4180 UR - https://www.unboundmedicine.com/medline/citation/32561270/Analysis_of_a_SARS_CoV_2_Infected_Individual_Reveals_Development_of_Potent_Neutralizing_Antibodies_with_Limited_Somatic_Mutation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7613(20)30231-4 DB - PRIME DP - Unbound Medicine ER -