SARS-CoV-2 Membrane protein-specific antibodies from critically ill SARS-CoV-2 infected individuals interact with Fc-receptor expressing cells, but do not neutralize the virus.

The membrane glycoprotein (M) of SARS-CoV-2 is one of the key viral proteins regulating virion assembly and morphogenesis. Immunologically, the M protein is a major source of peptide antigens driving T cell responses, and most individuals who have been infected with SARS-CoV-2 make antibodies to the N-terminal, surface-exposed peptide of the M protein. We now report that although the M protein is abundant in the viral particle, antibodies to the surface exposed N-terminal epitope of M do not appear to neutralise the virus. M protein-specific antibodies do, however, activate antibody-dependent cell-mediated cytotoxicity (ADCC) and cytokine secretion by primary human NK cells. Interestingly, while patients with severe or mild disease make comparable levels of M antigen-binding antibodies, M-specific antibodies from the serum of critically ill patients are significantly more potent activators of ADCC than antibodies found in individuals with mild or asymptomatic infection.