From trained immunity in allergy to trained immunity‐based allergen vaccines

Abstract

Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergenspecific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.

Training vs. Tolerance: The Yin/Yang of the Innate Immune System

“…Different ventures of existing vaccines or viral components to induce trained immunity seek to improve conventional vaccines toward the new formulations of the so-called trained immunity-based vaccines (TIbV), aimed at stimulating broader responses beyond their specific antigens, an approach that could make it possible to afford proper resistance against viral outbreaks [ 104 , 105 , 106 , 107 ]. However, this might not be the case for allergen vaccines.…”

“…However, this might not be the case for allergen vaccines. In a recent study Benito-Villalvilla et al, it was demonstrated that allergoid–mannan conjugates, which serve as next-generation vaccines for allergen-specific immunotherapy (AIT), contribute to allergen tolerance by the differentiation of monocytes into tolerogenic dendritic cells (DCs), but lack the capacity to induce any trained immunity effects [ 107 , 108 ]. Similarly, the innate counterparts of T cells—innate lymphoid cells (ILCs)—primed by IL-33 or allergic inflammation mount enduring memory-like responses against other allergens, which can serve as double-edged sword, on the one side affording proper protection against infectious diseases and, on the other side, by contributing to pathology or disease progression [ 109 , 110 , 111 ].…”

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

“…For example, the presence of stimuli such as dexamethasone (Dex), vitamin D3 (VitD3), rapamycin, or allergoid-mannan conjugates promotes the differentiation of monocytes into tolerogenic DCs or immunosuppressive macrophages ( 22 – 26 ). Conversely, monocytes exposed with whole heat-inactivated Candida albicans or β-glucans from its cell wall give raise to trained monocyte-derived macrophages ( 27 – 29 ). Here, we show that LPS-stimulated WIN-hmoDCs displayed reduced production of the pro-inflammatory cytokines TNFα, IL-1β and IL-6 without changes in IL-10.…”

Reprogramming dendritic cells through the immunological synapse: A two‐way street

“…Postsynaptic reprogramming could be useful during immunization, as innate training confers heterologous protection [68][69][70] from other diseases [71,72] due to the nonspecific trained immunity-based effect of vaccines [73,74]. Indeed, this effect could also increase the efficacy of existing vaccines [75], or bring forth a novel ground-breaking generation of trained immunitybased vaccines to fight infection [76][77][78][79][80] or allergy [81]. The underlying rationale would be that psDC could enhance innate and adaptive responses.…”