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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Bibliographic Details
Published in:	Microbiology spectrum Vol. 10; no. 1; p. e0267621
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 23-02-2022
Subjects:	Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antibodies, Viral - blood Antibodies, Viral - immunology Antibody Formation antibody neutralization convalescent-phase plasma COVID-19 COVID-19 - blood COVID-19 - immunology COVID-19 - virology Enzyme-Linked Immunosorbent Assay Host-Microbial Interactions Humans immunoassay Neutralization Tests Protein Domains Research Article SARS-CoV-2 SARS-CoV-2 - chemistry SARS-CoV-2 - genetics SARS-CoV-2 - immunology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - immunology spike protein COVID-19 SARS-CoV-2 spike glycoprotein receptor-binding domain spike protein antibody neutralization convalescent-phase plasma neutralizing antibodies N-terminal domain immunoglobulins adaptive immunity immunoassay
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Summary:	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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors declare no conflict of interest.
ISSN:	2165-0497 2165-0497
DOI:	10.1128/spectrum.02676-21