SARS-CoV-2 integral membrane proteins shape the serological responses of COVID-19 patients.

Martin, Sophie; Heslan, Christopher; Jégou, Gwénaële; Eriksson, Leif A.; Le Gallo, Matthieu; Thibault, Vincent; Chevet, Eric; Godey, Florence; Avril, Tony

SARS-CoV-2 pandemic has elicited a unique mobilization of the scientific community to develop efficient tools to understand and combat infection. Like other coronavirae, SARS-CoV-2 hijacks host cell secretory machinery to produce viral proteins that compose the nascent virions; including Spike (S), Envelope (E) and Membrane (M) proteins, the most exposed transmembrane proteins to the host immune system. As antibody response is part of the anti-viral immune arsenal, we investigate the immunogenic potential of S, E and M using a human cell-based system to mimic membrane insertion and N-glycosylation. Both S and M elicit specific Ig production in SARS-CoV-2 patients. Patients with moderate and severe diseases exhibit elevated Ig responses. Finally, reduced Ig binding was observed with Spike G614 compared to D614 variant. Altogether, our assay points towards an unexpected immune response against M and represents a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.