Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2.
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Bahnan W, Wrighton S, Sundwall M, Bläckberg A, Larsson O, Höglund U, Khakzad H, Godzwon M, Walle M, Elder E, Strand AS, Happonen L, André O, Ahnlide JK, Hellmark T, Wendel-Hansen V, Wallin RP, Malmstöm J, Malmström L, Ohlin M, Rasmussen M, Nordenfelt P
Front Immunol 12 (-) 808932
[2022-01-14; online 2022-01-14]
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.
Funder: KAW/SciLifeLab National COVID program
PubMed 35095897
DOI 10.3389/fimmu.2021.808932
Crossref 10.3389/fimmu.2021.808932