Novel adjuvants in allergen-specific immunotherapy: where do we stand? Yen-Ju Lin, Jennifer Zimmermann, and Stefan Schülke summarize the current state of adjuvants used in allergen-specific immunotherapy (AIT). AIT is the only disease-modifying treatment for type I allergies, which are caused by exaggerated immune responses against harmless environmental antigens. Conventional AIT has limitations, including long treatment durations, risk of allergic side effects, and low immunogenicity of allergens. Adjuvants can enhance immunogenicity and induce desired immune responses, such as Th1 or regulatory responses. The review discusses adjuvants currently approved for human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants like oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan), and TLR-ligands (flagellin and CpG-ODN). These adjuvants show distinct properties, such as prolonging allergen release, inducing IgG production while reducing IgE levels, and promoting immune cell differentiation and activation. Future research may improve AIT by better understanding the immunological mechanisms of these adjuvants. Key words: type I hypersensitivity, allergen-specific immunotherapy, adjuvant, CpG, virus-like particle, mannan, flagellin, Th1/Th2 responses. The review discusses the mechanisms of action of various adjuvants, including first- and second-generation adjuvants. First-generation adjuvants like aluminum salts, calcium phosphate, and microcrystalline tyrosine serve as carriers, adsorbing antigens and forming insoluble aggregates. These adjuvants activate immune cells, leading to cytokine secretion and inflammasome activation. Second-generation adjuvants, such as MPLA, activate immune cells by triggering PRRs, leading to transcriptional changes and enhanced antigen presentation. The review also discusses novel adjuvants like liposomes, virus-like particles, and carbohydrate-based adjuvants, which have shown potential in improving AIT. The current state of clinical investigation of these adjuvants is summarized in Table 1. The review highlights the potential of these adjuvants in improving AIT by enhancing immune responses and reducing allergic symptoms. However, further research is needed to fully understand their mechanisms and optimize their use in clinical settings.Novel adjuvants in allergen-specific immunotherapy: where do we stand? Yen-Ju Lin, Jennifer Zimmermann, and Stefan Schülke summarize the current state of adjuvants used in allergen-specific immunotherapy (AIT). AIT is the only disease-modifying treatment for type I allergies, which are caused by exaggerated immune responses against harmless environmental antigens. Conventional AIT has limitations, including long treatment durations, risk of allergic side effects, and low immunogenicity of allergens. Adjuvants can enhance immunogenicity and induce desired immune responses, such as Th1 or regulatory responses. The review discusses adjuvants currently approved for human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants like oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan), and TLR-ligands (flagellin and CpG-ODN). These adjuvants show distinct properties, such as prolonging allergen release, inducing IgG production while reducing IgE levels, and promoting immune cell differentiation and activation. Future research may improve AIT by better understanding the immunological mechanisms of these adjuvants. Key words: type I hypersensitivity, allergen-specific immunotherapy, adjuvant, CpG, virus-like particle, mannan, flagellin, Th1/Th2 responses. The review discusses the mechanisms of action of various adjuvants, including first- and second-generation adjuvants. First-generation adjuvants like aluminum salts, calcium phosphate, and microcrystalline tyrosine serve as carriers, adsorbing antigens and forming insoluble aggregates. These adjuvants activate immune cells, leading to cytokine secretion and inflammasome activation. Second-generation adjuvants, such as MPLA, activate immune cells by triggering PRRs, leading to transcriptional changes and enhanced antigen presentation. The review also discusses novel adjuvants like liposomes, virus-like particles, and carbohydrate-based adjuvants, which have shown potential in improving AIT. The current state of clinical investigation of these adjuvants is summarized in Table 1. The review highlights the potential of these adjuvants in improving AIT by enhancing immune responses and reducing allergic symptoms. However, further research is needed to fully understand their mechanisms and optimize their use in clinical settings.