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Adjuvants in allergen-specific immunotherapy: modulating and enhancing the immune response

Zubeldia JM1, Ferrer M2, Dávila I3, Justicia JL4

1 Allergy Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Gregorio Marañón Health Research Institute (IiSGM), Madrid, Spain. Biomedical Research Network on Rare Diseases (CIBERER)-U761, Madrid, Spain.
2 Department of Allergy, Clínica Universidad de Navarra, Pamplona, Spain. Department of Medical Education, School of Medicine, Navarra University, Pamplona, Spain.
3 Allergy Service, University Hospital of Salamanca, Salamanca, Spain. Department of Biomedical and Diagnostic Sciences, Faculty of Medicine of Salamanca, Salamanca, Spain. Institute for Biomedical Research, IBSAL, Salamanca, Spain.
4 Medical Department. Allergy Therapeutics Ibérica.

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

Allergen-specific immunotherapy (AIT) is the only treatment that may affect the natural course of allergic diseases such as allergic asthma, allergic rhinitis, and IgEmediated food allergy. Adjuvants are used to induce a quicker, more potent, and longer-lasting AIT immune response.
Up to now, only four compounds are used as adjuvants in currently marketed AIT products: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL). The three first adjuvants are delivery systems with depot effect, although they also may have immunomodulatory properties. These firstgeneration adjuvants are still widely used, especially aluminum hydroxide. However, aluminum has some limitations. MCT is the depot formulation of L-tyrosine; it enhances IgG production withoutinducing a significant IgE increase, 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, there are multiple adjuvants under research, including immunostimulatory sequences (ISS), nanoparticles (liposomes, virus-like particlesand biodegradable polymers), and phosphatidylserine derivatives.
In a murine model of allergic bronchial inflammation by sensitization to olive pollen, specific IgE level was significantly higher in sensitized mice treated with olive pollen and aluminum hydroxide. However, sensitized mice treated with olive pollen and bacterial derivatives (MPL or ISS) showed a significant reduction of specific IgE levels and a significant improvement of bronchial hyperreactivity.

Key words: Asthma, Allergen-specific immunotherapy, Adjuvant, Aluminum hydroxide, Calcium phosphate, Microcrystallinetyrosine, Monophosphoryllipid A, Immunostimulatorysequences, Nanoparticles