Rapid boosting increases germinal center responses to sequential vaccines

Area of Science:

• Immunology
• Vaccinology

Background:

• Germinal centers (GCs) are crucial for adaptive humoral immunity and antibody production.
• Understanding GC dynamics under changing antigen exposure is key for next-generation vaccine design, including germline targeting.

Purpose of the Study:

• To investigate the impact of rapid homologous and heterologous boosting on GC B-cell responses using HIV envelope immunogens in a mouse model.
• To explore how accelerated GC function can be leveraged for improved vaccine strategies.

Main Methods:

• Utilized a mouse model with human immunodeficiency virus (HIV) envelope surface protein immunogens.
• Administered rapid homologous and heterologous boosting strategies.
• Analyzed the expansion and evolution of GC B-cell populations and antibody affinity maturation.

Main Results:

• Rapid reimmunization led to significant expansion of on-target GC B-cell (B_GC) populations, primarily from existing B_GC cells.
• Early homologous boosting managed antibody titers and maximized B_GC response by utilizing off-target antibodies.
• Heterologous rapid boosting effectively shifted affinity maturation towards the new antigen.
• Sustained and rapidly evolving GCs achieved substantial affinity gains, binding wildtype HIV Env trimer within 56 days with minimal distinct antigens.

Conclusions:

• Accelerated GC responses through rapid boosting offer a promising strategy for enhancing vaccine efficacy.
• These findings provide critical insights into GC biology and demonstrate translatable pathways for leveraging accelerated GC function in vaccine development.