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Immunological effects of adjuvanted low‐dose allergoid allergen‐specific immunotherapy in experimental murine house dust mite allergy

Authors :
Matthias F. Kramer
Matthew D. Heath
Adam Chaker
Dennis Russkamp
Carsten B. Schmidt-Weber
Thalia L Carreno Velazquez
Ulrich M. Zissler
Murray A. Skinner
Sonja Heine
Simon Blank
Alexander Heldner
Francesca Alessandrini
Benjamin Schnautz
Juliet Mwange
Source :
Allergy, DOI: 10.1111/all.15012 (2021)
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

Background Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen-specific immunotherapy (AIT), although mechanistic side-by-side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high-dose HDM extract and low-dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy. Methods Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant-free intranasal sensitization followed by subcutaneous AIT. Results While low-dose allergoid and high-dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2-type cytokine secretion of lung-resident lymphocytes and draining lymph node cells, low-dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low-dose allergoid AIT with MCT or MCT and dose-adjusted MPL promoted Th1-inducing mechanisms and robust B-cell activation counterbalancing the allergic Th2 immune response. Conclusion Low allergen doses induce cellular and humoral mechanisms counteracting Th2-driven inflammation by using allergoids and dose-adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low-dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses.

Details

ISSN :
13989995 and 01054538
Volume :
77
Database :
OpenAIRE
Journal :
Allergy
Accession number :
edsair.doi.dedup.....da35a2109fdf301919407b89f848b115