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Adjuvants in Allergen-Specific Immunotherapy: Modulating and Enhancing the Immune Response

Zubeldia JM1, Ferrer M2, Dávila I3, Justicia JL4

1Allergy Service, Hospital General Universitario Gregorio Marañón; Gregorio Marañón Health Research Institute (IiSGM); Biomedical Research Network on Rare Diseases (CIBERER)-U761, Madrid, Spain
2Department of Allergy, Clínica Universidad de Navarra; Department of Medical Education, School of Medicine, Navarra University, Pamplona, Spain and Instituto de Investigación Sanitaria de Navarra (IdiSNA); RETIC de Asma, Reacciones adversas y Alérgicas (ARADYAL)
3Allergy Service, University Hospital of Salamanca; Department of Biomedical and Diagnostic Sciences, School of Medicine, University of Salamanca; Institute for Biomedical Research of Salamanca, Salamanca; Spain; RETIC de Asma, Reacciones adversas y Alérgicas (ARADYAL)
4Medical Department, Allergy Therapeutics Ibérica, Alcalá de Henares, Spain

J Investig Allergol Clin Immunol 2019; Vol 29(2) : 103-111
doi: 10.18176/jiaci.0349

Allergen-specific immunotherapy (AIT) is the only treatment that can affect the natural course of allergic diseases such as allergic asthma, allergic rhinitis, and IgE-mediated food allergy. Adjuvants are used to induce a quicker, more potent, and longer-lasting immune response.  Only 4 compounds are used as adjuvants in currently marketed AIT products: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL). The first 3 adjuvants are delivery systems with a depot effect, although they may also have immunomodulatory properties. These first-generation adjuvants are still widely used, especially aluminum hydroxide. However, aluminum is subject to limitations. MCT is the depot formulation of L-tyrosine; it enhances IgG production without inducing a significant increase in IgE, is biodegradable, and has good local and systemic tolerability. In turn, MPL is an immunostimulatory agent that is the only second-generation adjuvant currently used for AIT. In addition, multiple adjuvants are currently being studied, including immunostimulatory sequences (ISSs), nanoparticles (liposomes, virus-like particles, and biodegradable polymers), and phosphatidylserine derivatives.
In a murine model of allergic bronchial inflammation by sensitization to olive pollen, the specific IgE level was significantly higher in sensitized mice treated with olive pollen and aluminum hydroxide. However, specific IgE levels were significantly reduced and bronchial hyperreactivity significantly improved in sensitized mice treated with olive pollen and bacterial derivatives (MPL or ISSs).

Key words: Asthma, Allergen-specific immunotherapy, Adjuvant, Aluminum hydroxide, Calcium phosphate, Microcrystalline tyrosine, Monophosphoryl lipid A, Immunostimulatory sequences, Nanoparticles