Pre-existing immunity modulates responses to mRNA boosters

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• Severe COVID-19 is preventable with mRNA vaccines, but boosters are needed due to breakthrough infections, variants, and waning immunity.
• The impact of pre-existing immunity on mRNA vaccine booster efficacy is not fully understood.
• Current mRNA booster strategies are being implemented globally.

Purpose of the Study:

• To investigate how pre-existing immunity influences the immunogenicity of mRNA vaccine boosters.
• To elucidate the mechanisms by which pre-existing antibodies affect booster responses.
• To explore strategies for potentially improving mRNA booster efficacy.

Main Methods:

• Analysis of antibody levels in individuals receiving mRNA-1273 or BNT162b2 vaccines before and after booster doses.
• Studies in a mouse model to assess the impact of pre-existing antibodies on vaccine antigen clearance and B cell responses.
• Investigation of Fc-dependent mechanisms involved in antigen clearance.

Main Results:

• Lower pre-booster antibody levels correlated with a greater fold-increase in antibodies post-boost in humans.
• Pre-existing antibodies in mice accelerated vaccine antigen clearance through Fc-dependent pathways.
• This accelerated clearance limited the antigen available for priming de novo B cell responses.

Conclusions:

• Pre-existing antibodies modulate the immunogenicity of mRNA vaccine boosters, creating a 'tug of war' with new B cell responses.
• Transiently reducing antibody effector function might enhance the effectiveness of mRNA vaccine boosters.
• Further research is warranted to explore therapeutic strategies targeting antibody effector functions for improved vaccination outcomes.