Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

Antibodies to the RBD of SARS-CoV-2 spike mediate productive infection of primary human macrophages.

Publication date: Dec 30, 2024

The role of myeloid cells in the pathogenesis of SARS-CoV-2 is well established, in particular as drivers of cytokine production and systemic inflammation characteristic of severe COVID-19. However, the potential for myeloid cells to act as bona fide targets of productive SARS-CoV-2 infection, and the specifics of entry, remain unclear. Using a panel of anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed a detailed assessment of antibody-mediated infection of monocytes/macrophages. mAbs with the most consistent potential to mediate infection were those targeting a conserved region of the receptor binding domain (RBD; group 1/class 4). Infection was closely related to the neutralising concentration of the mAbs, with peak infection occurring below the IC50, while pre-treating cells with remdesivir or FcγRI-blocking antibodies inhibited infection. Studies performed in primary macrophages demonstrated high-level and productive infection, with infected macrophages appearing multinucleated and syncytial. Infection was not seen in the absence of antibody with the same quantity of virus. Addition of ruxolitinib significantly increased infection, indicating restraint of infection through innate immune mechanisms rather than entry. High-level production of pro-inflammatory cytokines directly correlated with macrophage infection levels. We hypothesise that infection via antibody-FcR interactions could contribute to pathogenesis in primary infection, systemic virus spread or persistent infection.

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Concepts Keywords
Antibodies Adenosine Monophosphate
Ic50 Adenosine Monophosphate
Myeloid Alanine
Pro Alanine
Ruxolitinib Antibodies, Monoclonal
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Neutralizing
Antibodies, Viral
Antibodies, Viral
Cells, Cultured
COVID-19
Humans
Macrophages
Nitriles
Nitriles
Protein Domains
Pyrazoles
Pyrazoles
Pyrimidines
Pyrimidines
Receptors, IgG
Receptors, IgG
remdesivir
ruxolitinib
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Virus Internalization

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