SARS-CoV-2 Membrane protein-specific antibodies from critically ill COVID-19-infected individuals are potent stimulators of NK cell activation
Year: 2022
Type: conference-abstract
Abstract: Introduction. The M glycoprotein is the most abundant structural protein of the SARS-CoV-2 particle and is one of the key components for virion assembly and morphogenesis. It is a major source of peptide antigens driving T-cell responses and previous studies have shown that most patients make antibodies against its N-terminal domain.Nevertheless, no studies of the function of M-specific antibodies have been reported. Materials and Methods. We expressed the first 23 amino-acids of the M protein as a GST-fusion protein in E.coli. Sera from 37 COVID-19 patients (20 of them critically ill, admitted to ICU; 17 of them with mild disease) were assayed in a standard ELISA assay to detect reactive antibodies. The neutralization capacity of M-specific antibodies was assessed in neutralization experiments against SARS-CoV-2 virus using polyclonal antibodies purified by affinity chromatography from patient sera, while the ability of the antibodies in patients’ sera to activate Natural Killer cells was measured in an ELISA-based assay in which antigen-bound antibodies were incubated with PBMC and NK cell activation was detected by flow cytometry. Results. We could detect M-specific antibodies in most of the patients, and they could discriminate between infected and non-infected individuals with around 90% efficacy. No significant difference in the quantity of the antibody response was found between mild and critical patients. No polyclonal M-specific antibodies showed neutralization activity in the in vitro system used. Nevertheless, when PBMC from healthy donors were incubated with patients’ M- specific antibodies bound to the GST-M fusion protein in an ELISA plate, NK cells were significantly activated, as measured by LAMP1+ degranulation and cytokine (MIP1β) production. Conclusion. We show that most SARS-CoV-2 infected individuals produce specific antibodies against a surfaceexposed epitope at the N-terminus of M glycoprotein. Although these antibodies do not appear to neutralize the virus efficiently, they are able to mediate Fc/FcγR interactions to drive the activation of NK cells.
Source: IBJ Plus
Authors: Daniel Fernández-Soto, Paula Bueno, Urtzi Garaigorta, Pablo Gastaminza, José L Bueno, Rafael F Duarte, Ricardo Jara, Immunostep, S.L., Centro Investigación del Cáncer (CIC), Salamanca, Spain., Mar Valés-Gómez, Hugh T Reyburn
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: Fundación Ramón Areces, Fundació la Marató de TV3, Banco Santander, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, Centro de Biología Molecular Severo Ochoa, AXA Research Fund, Ministerio de Educación, Cultura y Deporte, Novo Nordisk, Universidad Autónoma de Madrid, Ministerio de Ciencia e Innovación, Ministerio de Ciencia y Tecnología, Novo Nordisk Fonden, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Consejería de Educación e Investigación, Centro de Investigación Biomédica en Red de Cáncer, Agencia Nacional de Investigación y Desarrollo, Centers for Disease Control and Prevention, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, European Regional Development Fund, Dirección General de Universidades e Investigación, Agencia Estatal de Investigación, European Social Fund
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OpenAlex ID: W4282573823