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

Bahnan, W.; Wrighton, S.; Sundwall, M.; Bläckberg, A.; Larsson, O.; Höglund, U.; Khakzad, H.; Godzwon, M.; Walle, M.; Elder, E.; Happonen, L.; Andre, O.; Kumra Ahnlide, J.; Hellmark, T.; Wendel-Hansen, V.; Wallin, R. P.; Malmström, J.; Malmström, L.; Ohlin, M.; Rasmussen, M.; Nordenfelt, P.

doi:10.1101/2021.10.14.464464

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bioRxiv · 10.1101/2021.10.14.464464

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

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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 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 phago-cytosis.

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Bahnan, W., Wrighton, S., Sundwall, M., Bläckberg, A., Larsson, O., Höglund, U., Khakzad, H., Godzwon, M., Walle, M., Elder, E., Happonen, L., Andre, O., Kumra Ahnlide, J., Hellmark, T., Wendel-Hansen, V., Wallin, R. P., Malmström, J., Malmström, L., Ohlin, M., Rasmussen, M., Nordenfelt, P.. 2021-10-15. Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis. https://doi.org/10.1101/2021.10.14.464464

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