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Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target th...

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Autores principales: Van Ert, Hanora A., Bohan, Dana W., Rogers, Kai, Fili, Mohammad, Rojas Chávez, Roberth A., Qing, Enya, Han, Changze, Dempewolf, Spencer, Hu, Guiping, Schwery, Nathan, Sevcik, Kristina, Ruggio, Natalie, Boyt, Devlin, Pentella, Michael A., Gallagher, Tom, Jackson, J. Brooks, Merrill, Anna E., Knudson, C. Michael, Brown, Grant D., Maury, Wendy, Haim, Hillel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791189/
https://www.ncbi.nlm.nih.gov/pubmed/35080430
http://dx.doi.org/10.1128/spectrum.02676-21
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author Van Ert, Hanora A.
Bohan, Dana W.
Rogers, Kai
Fili, Mohammad
Rojas Chávez, Roberth A.
Qing, Enya
Han, Changze
Dempewolf, Spencer
Hu, Guiping
Schwery, Nathan
Sevcik, Kristina
Ruggio, Natalie
Boyt, Devlin
Pentella, Michael A.
Gallagher, Tom
Jackson, J. Brooks
Merrill, Anna E.
Knudson, C. Michael
Brown, Grant D.
Maury, Wendy
Haim, Hillel
author_facet Van Ert, Hanora A.
Bohan, Dana W.
Rogers, Kai
Fili, Mohammad
Rojas Chávez, Roberth A.
Qing, Enya
Han, Changze
Dempewolf, Spencer
Hu, Guiping
Schwery, Nathan
Sevcik, Kristina
Ruggio, Natalie
Boyt, Devlin
Pentella, Michael A.
Gallagher, Tom
Jackson, J. Brooks
Merrill, Anna E.
Knudson, C. Michael
Brown, Grant D.
Maury, Wendy
Haim, Hillel
author_sort Van Ert, Hanora A.
collection PubMed
description The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.
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spelling pubmed-87911892022-02-09 Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein Van Ert, Hanora A. Bohan, Dana W. Rogers, Kai Fili, Mohammad Rojas Chávez, Roberth A. Qing, Enya Han, Changze Dempewolf, Spencer Hu, Guiping Schwery, Nathan Sevcik, Kristina Ruggio, Natalie Boyt, Devlin Pentella, Michael A. Gallagher, Tom Jackson, J. Brooks Merrill, Anna E. Knudson, C. Michael Brown, Grant D. Maury, Wendy Haim, Hillel Microbiol Spectr Research Article The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response. American Society for Microbiology 2022-01-26 /pmc/articles/PMC8791189/ /pubmed/35080430 http://dx.doi.org/10.1128/spectrum.02676-21 Text en Copyright © 2022 Van Ert et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Van Ert, Hanora A.
Bohan, Dana W.
Rogers, Kai
Fili, Mohammad
Rojas Chávez, Roberth A.
Qing, Enya
Han, Changze
Dempewolf, Spencer
Hu, Guiping
Schwery, Nathan
Sevcik, Kristina
Ruggio, Natalie
Boyt, Devlin
Pentella, Michael A.
Gallagher, Tom
Jackson, J. Brooks
Merrill, Anna E.
Knudson, C. Michael
Brown, Grant D.
Maury, Wendy
Haim, Hillel
Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title_full Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title_fullStr Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title_full_unstemmed Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title_short Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
title_sort limited variation between sars-cov-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791189/
https://www.ncbi.nlm.nih.gov/pubmed/35080430
http://dx.doi.org/10.1128/spectrum.02676-21
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