Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
| Autor: | Wael, Bahnan, Sebastian, Wrighton, Martin, Sundwall, Anna, Bläckberg, Olivia, Larsson, Urban, Höglund, Hamed, Khakzad, Magdalena, Godzwon, Maria, Walle, Elisabeth, Elder, Anna Söderlund, Strand, Lotta, Happonen, Oscar, André, Johannes Kumra, Ahnlide, Thomas, Hellmark, Vidar, Wendel-Hansen, Robert Pa, Wallin, Johan, Malmstöm, Lars, Malmström, Mats, Ohlin, Magnus, Rasmussen, Pontus, Nordenfelt |
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| Rok vydání: | 2021 |
| Předmět: |
SARS-CoV-2
Immunology Antibodies Monoclonal COVID-19 phagocytosis Antibodies Viral Antibodies Neutralizing Cell Line HEK293 Cells Neutralization Tests Opsonization Spike Glycoprotein Coronavirus antibody binding Humans antibodies SARS – CoV – 2 antibody function spike (S) protein in vivo model Original Research |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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