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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2

Bahnan, Wael LU ; Wrighton, Sebastian LU orcid ; Sundwall, Martin LU orcid ; Bläckberg, Anna LU ; Larsson, Olivia ; Höglund, Urban ; Khakzad, Hamed ; Godzwon, Magdalena LU orcid ; Walle, Maria LU and Elder, Elisabeth , et al. (2022) In Frontiers in Immunology 12.
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SARS-CoV-2, COVID-19
in
Frontiers in Immunology
volume
12
article number
808932
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85123794692
  • pmid:35095897
ISSN
1664-3224
DOI
10.3389/fimmu.2021.808932
language
English
LU publication?
yes
id
014d014e-4a07-4d4f-9d94-15d649e06b3c
date added to LUP
2022-02-01 09:51:35
date last changed
2025-04-04 13:58:05
@article{014d014e-4a07-4d4f-9d94-15d649e06b3c,
  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 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.}},
  author       = {{Bahnan, Wael and Wrighton, Sebastian and Sundwall, Martin and Bläckberg, Anna and Larsson, Olivia and Höglund, Urban and Khakzad, Hamed and Godzwon, Magdalena and Walle, Maria and Elder, Elisabeth and Strand, Anna Söderlund and Happonen, Lotta and André, Oscar and Ahnlide, Johannes Kumra and Hellmark, Thomas and Wendel-Hansen, Vidar and Wallin, Robert Pa. and Malmstöm, Johan and Malmström, Lars and Ohlin, Mats and Rasmussen, Magnus and Nordenfelt, Pontus}},
  issn         = {{1664-3224}},
  keywords     = {{SARS-CoV-2; COVID-19}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2021.808932}},
  doi          = {{10.3389/fimmu.2021.808932}},
  volume       = {{12}},
  year         = {{2022}},
}