RBD-Based ELISA and luminex predict Anti-SARS-CoV-2 surrogate-neutralizing activity in two longitudinal cohorts of German and Spanish health care workers

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• dc.contributor.author Aguilar, Ruth
• dc.contributor.author Vidal, Marta
• dc.contributor.author Rubio, Rocío
• dc.contributor.author Jiménez, Alfons
• dc.contributor.author Carolis, Carlo
• dc.contributor.author Mayor, Alfredo
• dc.contributor.author Izquierdo, Luis
• dc.contributor.author Garcia Basteiro, Alberto L.
• dc.contributor.author Moncunill, Gemma
• dc.contributor.author Dobaño, Carlota
• dc.contributor.author Gerhard, Markus
• dc.date.accessioned 2023-03-17T07:15:48Z
• dc.date.available 2023-03-17T07:15:48Z
• dc.date.issued 2023
• dc.description.abstract The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity. We measured IgG levels against SARS-CoV-2 spike protein (S), its S2 subunit, the S1 receptor binding domain (RBD), and the full length and C terminus of nucleocapsid (N) protein by Luminex, and against RBD by enzyme-linked immunosorbent assay (ELISA), and assessed those as predictors of plasma surrogate-neutralizing activity measured by a flow cytometry assay. In addition, we determined the clinical and demographic factors affecting plasma surrogate-neutralizing capacity. Both cohorts showed a high positive correlation between IgG levels to S antigen, especially to RBD, and the levels of plasma surrogate-neutralizing activity, suggesting RBD IgG as a good correlate of plasma neutralizing activity. Symptomatic infection, with symptoms such as loss of taste, dyspnea, rigors, fever and fatigue, was positively associated with anti-RBD IgG positivity by ELISA and Luminex, and with plasma surrogate-neutralizing activity. Our serological assays allow for the prediction of serum neutralization activity without the cost, hazards, time, and expertise needed for surrogate or conventional neutralization assays. Once a cutoff is established, these relatively simple high-throughput antibody assays will provide a fast and cost-effective method of assessing levels of protection from SARS-CoV-2 infection. IMPORTANCE Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level. Serological tests could be an alternative if they are proved to be good predictors of plasma neutralizing activity. In this study, we analyzed the SARS-CoV-2 serological profiles of two cohorts of health care workers by applying Luminex and ELISA in-house serological assays. Correlations of both serological tests were assessed between them and with a flow cytometry assay to determine plasma surrogate-neutralizing activity. Both assays showed a high positive correlation between IgG levels to S antigens, especially RBD, and the levels of plasma surrogate-neutralizing activity. This result suggests IgG to RBD as a good correlate of plasma surrogate-neutralizing activity and indicates that serology of IgG to RBD could be used to assess levels of protection from SARS-CoV-2 infection.
• dc.description.sponsorship This work was supported by the European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Program. The study was also supported by the Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona and the Fundació Privada Daniel Bravo Andreu. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. L.I. was supported by the PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. R.R. had the support of the Health Department, Catalan Government (PERIS SLT017/20/000224). Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C).
• dc.format.mimetype application/pdf
• dc.identifier.citation Aguilar R, Li X, Crowell CS, Burrell T, Vidal M, Rubio R, et al. RBD-Based ELISA and luminex predict Anti-SARS-CoV-2 surrogate-neutralizing activity in two longitudinal cohorts of German and Spanish health care workers. Microbiol Spectr. 2023 Feb 14;11(1):e0316522. DOI: 10.1128/spectrum.03165-22
• dc.identifier.doi http://dx.doi.org/10.1128/spectrum.03165-22
• dc.identifier.issn 2165-0497
• dc.identifier.uri http://hdl.handle.net/10230/56248
• dc.language.iso eng
• dc.publisher American Society for Microbiology
• dc.relation.ispartof Microbiology Spectrum. 2023 Feb 14;11(1):e0316522
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110810RB-I00
• dc.rights © 2023 Aguilar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ELISA
• dc.subject.keyword Luminex
• dc.subject.keyword SARS-CoV-2
• dc.subject.keyword Antibodies
• dc.subject.keyword Immunoglobulin G
• dc.subject.keyword Neutralization
• dc.subject.keyword Receptor binding domain
• dc.subject.keyword Spike protein
• dc.subject.keyword Symptoms
• dc.title RBD-Based ELISA and luminex predict Anti-SARS-CoV-2 surrogate-neutralizing activity in two longitudinal cohorts of German and Spanish health care workers
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion