Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
Keywords: SARS – CoV – 2; antibodies; antibody binding; antibody function; in vivo model; phagocytosis; spike (S) protein.
Copyright © 2022 Bahnan, Wrighton, Sundwall, Bläckberg, Larsson, Höglund, Khakzad, Godzwon, Walle, Elder, Strand, Happonen, André, Ahnlide, Hellmark, Wendel-Hansen, Wallin, Malmstöm, Malmström, Ohlin, Rasmussen and Nordenfelt.