Highly active engineered IgG3 antibodies against SARS-CoV-2.

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• Monoclonal antibodies (mAbs) are crucial for neutralizing SARS-CoV-2, but their functions beyond antigen binding are not fully understood.
• Understanding the diverse roles of antibodies in SARS-CoV-2 immunity is essential for effective therapeutic and vaccine development.

Purpose of the Study:

• To explore the diverse functions of different antibody (Ab) subclasses in SARS-CoV-2 immunity.
• To investigate the neutralization potency of various IgG subclasses against SARS-CoV-2 spike protein (SP).

Main Methods:

• Expressed four human IgG subclasses (IgG1-4) of a SARS-CoV-2 SP-binding mAb (H4) in glyco-engineered *Nicotiana benthamiana* plants.
• Analyzed antibody assembly, glycosylation profiles, and binding activity to the SP.
• Assessed the neutralization potency of each H4 subclass against SARS-CoV-2.

Main Results:

• All four H4 IgG subclasses were successfully expressed in planta with a homogeneous, xylose- and fucose-free glycosylation profile.
• IgG3 subclass showed up to a fivefold increase in binding activity to the SP compared to other subclasses.
• H4-IgG3 demonstrated up to 50-fold superior neutralization potency against SARS-CoV-2 compared to other IgG subclasses.

Conclusions:

• IgG3 antibodies exhibit a strong protective effect against SARS-CoV-2 infection, likely due to enhanced neutralization via SP cross-linking.
• These findings highlight the therapeutic potential of IgG3 antibodies and inform vaccine development strategies.
• Plant-based expression systems offer a versatile platform for rapid production of complex therapeutic proteins during emergencies.