How to Employ Trained Immunity and Trained Immunity-Based Vaccines to Inhibit Allergic Inflammation.

Trained immunity confers protection against subsequent unrelated infections through metabolic and epigenetic reprogramming. Unlike adaptive immunity, trained innate immunity provides broad, non-specific protection against diverse heterologous pathogens. In addition to potentiating inflammatory responses upon secondary challenge, trained innate immune cells can also acquire anti-inflammatory and tolerogenic phenotypes, a property with important implications for chronic inflammatory diseases such as allergic disorders. Trained immunity-based vaccines (TIbVs) have emerged as promising immunomodulatory strategies capable of attenuating allergic inflammation by inducing immune tolerance. Similarly, allergen-specific immunotherapy (AIT) promotes long-term tolerance to allergens through metabolic and epigenetic reprogramming of innate immune cells. AIT drives the differentiation of monocytes into tolerogenic dendritic cells, thereby reshaping downstream adaptive immune responses. This review summarizes the current understanding of trained immunity and its role in protection against the same and heterologous infections. We discuss the molecular mechanisms underlying trained immunity, with an emphasis on metabolic and epigenetic reprogramming. Furthermore, we highlight the therapeutic potential of TIbVs and AIT as next-generation vaccines for allergic diseases. A deeper understanding of AIT-induced immune tolerance, the identification of predictive biomarkers, and the optimization of delivery platforms-such as lipid nanoparticle-based systems-will be critical for improving the safety and efficacy of future anti-allergy vaccines.