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
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.
Subject
Immunology,Immunology and Allergy