Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis

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 b...

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Bibliographic Details
Published in:bioRxiv 2021-10
Main Authors: Bahnan, Wael, Wrighton, Sebastian, Sundwall, Martin, Bläckberg, Anna, Larsson, Olivia, Höglund, Urban, Khakzad, Hamed, Godzwon, Magdalena, Walle, Maria, Elder, Elizabeth, Happonen, Lotta, André, Oscar, Johannes Kumra Ahnlide, Hellmark, Thomas, Wendel-Hansen, Vidar, Wallin, Robert Pa, Malmström, Johan, Malmström, Lars, Ohlin, Mats, Rasmussen, Magnus, Nordenfelt, Pontus
Format: Article
Language:English
Subjects:
ACE2
Angiotensin-converting enzyme 2
Antibodies
COVID-19
Monoclonal antibodies
Monocytes
Opsonization
Phagocytosis
Severe acute respiratory syndrome coronavirus 2
Spike protein
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Summary: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 seems to affect 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.10.14.464464