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Heldner, A. ; Alessandrini, F. ; Russkamp, D. ; Heine, S. ; Schnautz, B. ; Chaker, A. ; Mwange, J.* ; Carreno Velazquez, T.L.* ; Heath, M.D.* ; Skinner, M.A.* ; Kramer, M.F.* ; Zissler, U.M. ; Schmidt-Weber, C.B. ; Blank, S.

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

Allergy, DOI: 10.1111/all.15012 (2021)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adjuvant ; Allergen Extract ; Allergen-specific Immunotherapy ; Allergoid ; House Dust Mite Allergy; Monophosphoryl-lipid-a; T-cell Responses; Subcutaneous Immunotherapy; Mpl(r); Tolerance; Vaccines; Antibody; Tyrosine; Model; Immunogenicity
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Grants Allergy Therapeutics plc.
Helmholtz-Gemeinschaft