Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein
Date
2022-01-26
Authors
Van Ert, Hanora A.
Bohan, Dana W.
Rogers, Kai
Fili, Mohammad
Rojas Chávez, Roberth A.
Qing, Enya
Han, Changze
Dempewolf, Spencer
Schwery, Nathan
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract
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.
Series Number
Journal Issue
Is Version Of
Versions
Series
Academic or Administrative Unit
Type
article
Comments
This article is published as Van Ert, Hanora A., Dana W. Bohan, Kai Rogers, Mohammad Fili, Roberth A. Rojas Chávez, Enya Qing, Changze Han et al. "Limited variation between SARS-CoV-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein." Microbiology Spectrum 10, no. 1 (2022): e02676-21.
DOI: 10.1128/spectrum.02676-21.
Copyright 2022 Van Ert et al.
Attribution 4.0 International (CC BY 4.0).
Posted with permission.