Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• The emergence of novel coronaviruses (CoVs), exemplified by severe acute respiratory syndrome (SARS)-CoV-2, underscores the urgent requirement for broad-spectrum antiviral therapies and vaccines.
• Coronaviruses pose a significant global health threat, necessitating research into cross-reactive immune responses and therapeutic targets.

Purpose of the Study:

• To identify and characterize monoclonal antibodies with cross-reactivity against various CoV spike (S) proteins, particularly SARS-CoV and SARS-CoV-2.
• To investigate the epitopes recognized by these antibodies on the SARS-CoV-2 S protein and their functional capabilities.
• To evaluate the therapeutic potential of these antibodies in vivo for mitigating CoV-induced pathology.

Main Methods:

• Isolation and characterization of six monoclonal antibodies from a SARS-CoV donor sample.
• Epitope mapping to identify binding sites on the SARS-CoV-2 S protein (receptor-binding domain, N-terminal domain, S2 subunit).
• In vitro functional assays (phagocytosis, trogocytosis, neutralization) and in vivo studies in murine models of lung pathology.

Main Results:

• A panel of six monoclonal antibodies demonstrated cross-reactivity with SARS-CoV and SARS-CoV-2 S proteins, with varying reactivity against other CoVs.
• Antibodies recognized multiple epitopes on the SARS-CoV-2 S protein, including the receptor-binding domain, N-terminal domain, and S2 subunit.
• In vitro, antibodies mediated phagocytosis and trogocytosis but not neutralization; in vivo, two antibodies reduced lung hemorrhagic pathology in murine models.

Conclusions:

• The identified monoclonal antibodies offer potential as broadly reactive therapeutic agents against coronaviruses.
• The cross-reactive epitopes identified provide valuable targets for the development of pan-coronavirus vaccines.
• This research expands the understanding of antibody-mediated immunity and therapeutic strategies for coronavirus infections.