FIG 2.

Approaches to maximize the safety and efficacy of immunotherapy with food allergens. Immunotherapy with native antigen results in side effects caused by activation of allergic effector cells and a modification of the adaptive T-cell response to enhance Treg cells and suppress T_H2 cells. Approaches to increase safety by reducing the activation of allergic effector cells includes using peptides that cannot cross-link IgE, modifying the allergens (by heating or mannosylation), binding to particles like syngeneic leukocytes, and encapsulating in nanoparticles or within microbial carriers. Approaches to boost the immunomodulatory effects on the adaptive immune response include modifying the antigen to provide adjuvants that act on antigen-presenting cells (mannosylation and Toll-like receptor ligands), binding to syngeneic leukocytes (providing tolerogenic cues), or encapsulating the antigen together with microbial adjuvants. Studies are needed to test the effect of adding novel immunomodulatory agents (tolerogenic adjuvants or neutralizing antibodies that target antigen presenting cells) to immunotherapy protocols.