IgG3 collaborates with IgG1 and IgA to recruit effector function in RV144 vaccinees

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• The RV144 HIV vaccine trial demonstrated moderate efficacy, but correlates of protection require further investigation, especially in light of new data.
• Understanding the interplay of antibody subclasses and isotypes induced by vaccines is critical for improving HIV vaccine design.

Purpose of the Study:

• To comprehensively profile the humoral immune response in RV144 vaccinees.
• To decipher the relationships between antibody biomarkers and protection against HIV acquisition.

Main Methods:

• Analysis of humoral immune responses in 300 RV144 vaccinees.
• Profiling of vaccine-specific IgG1, IgG3, and IgA antibody levels and functions.
• Case/control analysis to assess antibody-driven functions in infected versus non-infected vaccinees.

Main Results:

• Vaccine-specific IgG1, IgG3, and IgA antibodies were highly correlated.
• IgG3 function was dependent on IgG1 levels, indicating a collaborative role.
• Higher IgA levels correlated with enhanced effector functions but were associated with increased infection in some cases, suggesting potential immune compromise.

Conclusions:

• The interplay between IgG1, IgG3, and IgA is critical for effective antiviral humoral immunity.
• IgG3 is a key contributor, but not the sole driver, of protection.
• IgA-driven effector functions may compromise vaccine-induced immunity, necessitating careful consideration of subclass/isotype selection in vaccine development.