AUTHOR=Bahnan Wael , Wrighton Sebastian , Sundwall Martin , Bläckberg Anna , Larsson Olivia , Höglund Urban , Khakzad Hamed , Godzwon Magdalena , Walle Maria , Elder Elisabeth , Strand Anna Söderlund , Happonen Lotta , André Oscar , Ahnlide Johannes Kumra , Hellmark Thomas , Wendel-Hansen Vidar , Wallin Robert PA. , Malmstöm Johan , Malmström Lars , Ohlin Mats , Rasmussen Magnus , Nordenfelt Pontus TITLE=Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2 JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.808932 DOI=10.3389/fimmu.2021.808932 ISSN=1664-3224 ABSTRACT=

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.