IgG4 Neutralization and Sustained Total IgG Fc-Effector Functions Following Repeated SARS-CoV-2 Vaccination with...

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• SARS-CoV-2 mRNA vaccines elicit diverse antibody profiles, including immunoglobulin G (IgG) subclasses.
• Repeat dosing of mRNA vaccines leads to increased antigen-specific IgG4 antibodies.
• The functional role of IgG4 antibodies in SARS-CoV-2 mRNA vaccine immunity is not fully understood.

Purpose of the Study:

• To investigate the dynamics of IgG subclass responses after Moderna mRNA-1273 vaccination.
• To assess IgG Fc-mediated functions and neutralization capacity following vaccination.
• To determine the impact of elevated IgG4 levels on overall vaccine-induced immunity.

Main Methods:

• Tracking of IgG subclass levels, Fc-mediated functions, and neutralization.
• Analysis of antibody responses after two or three doses of Moderna mRNA-1273 vaccine.
• Evaluation of healthy adult participants.

Main Results:

• Robust IgG1 and IgG3 responses were observed, with a significant increase in IgG4 after repeated dosing.
• Elevated IgG4 levels did not impair Fc-effector functions (e.g., phagocytosis, complement deposition).
• IgG4 antibodies demonstrated enhanced affinity and potent neutralization capabilities, complementing IgG1 responses.

Conclusions:

• Increased IgG4 antibody levels following mRNA-1273 vaccination do not antagonize Fc-mediated effector mechanisms.
• Moderna mRNA-1273 induces a multi-subclass antibody response that maintains antiviral functionality.
• The study suggests a preserved antiviral capacity despite elevated IgG4 responses.