Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.808932
Keywords
antibodies; SARS; CoV; 2; antibody function; antibody binding; spike (S) protein; phagocytosis; in vivo model
Categories
Funding
- Knut and Alice Wallenberg Foundation
- IngaBritt och Arne Lundbergs Forskningsstiftelse
- SciLifeLab National COVID-19 Research Program - Knut and Alice Wallenberg Foundation
- Royal Physiographic Society
- Swiss National Science Foundation [P2ZHP3_191289]
- Swiss National Science Foundation (SNF) [P2ZHP3_191289] Funding Source: Swiss National Science Foundation (SNF)
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The concentration of Spike-specific antibodies can enhance or reduce Spike-bead phagocytosis by monocytes, independent of antibody neutralization potential. The levels of anti-Spike antibodies correlate with the outcome in an experimental SARS-CoV-2 infection model, suggesting that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating 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 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.
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