Seasonal variation in BCG-induced trained immunity

Area of Science:

• Immunology
• Vaccinology
• Chronobiology

Background:

• Bacille Calmette-Guerin (BCG) vaccine induces trained immunity, enhancing innate immune responses.
• Seasonal variations are known to influence innate immunity, but their impact on BCG-induced trained immunity remains unexplored.

Purpose of the Study:

• To investigate the influence of vaccination season (winter vs. spring) on BCG-induced trained immunity.
• To analyze ex vivo cytokine responses, gene expression, and epigenetic signatures in immune cells post-BCG vaccination.

Main Methods:

• Healthy volunteers were vaccinated with BCG during winter or spring.
• Three months post-vaccination, peripheral blood mononuclear cells (PBMCs) and NK cells were analyzed for cytokine production, gene expression, and epigenetic modifications.
• Responses were compared to baseline and between vaccination groups.

Main Results:

• Winter BCG vaccination induced a stronger pro-inflammatory cytokine response in PBMCs compared to spring vaccination.
• NK cells from winter-vaccinated individuals showed enhanced pro-inflammatory cytokine and IFNγ production capacity.
• Season-dependent epigenetic changes were identified in monocytes and NK cells, correlating with enhanced immune cell reactivity in the winter group.

Conclusions:

• BCG vaccination during winter promotes a more robust trained immunity response than spring vaccination.
• Seasonal timing influences BCG's ability to activate and epigenetically reprogram immune cells, particularly NK cells.
• Findings suggest optimizing vaccination timing for enhanced innate immune memory induction.