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

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.

The grass pollen season 2014 in Vienna: A pilot study combining phenology, aerobiology and symptom data.

BACKGROUND: Grasses (Poaceae) are one of the largest plant families and are distributed worldwide. Grass pollen allergy is one of the most important pollen allergies affecting large parts of the population worldwide. The grass pollen season itself is special since it is caused by the flowering of various grass species that present unique profiles of allergenicity, which assumingly plays a significant role and impact on grass pollen sensitization profiles for the allergy sufferer. The aim of this study, conducted in Vienna, 2014, was to analyze the possible contribution of prevalent grass species to the grass pollen season and to the symptom load of grass allergy sufferers. METHODS: This was the first study that combines phenological observations (i.e. grass species and their flowering periods) with aerobiological measurements (i.e. daily grass pollen concentrations) in concert with allergic symptoms from local users of the Patient's Hayfever Diary (symptom load index calculation). RESULTS: Both the pollen concentrations and the symptom levels were higher in the first half of the main grass pollen season and therefore show the highest impact on pollen allergy sufferers. Of important note were the following species that are widely distributed in Vienna: Kentucky bluegrass (Poa pratensis), orchard grass (Dactylis glomerata), false oat-grass (Arrhenatherum elatius), fescue grass (Festuca sp.) and perennial rye-grass (Lolium perenne). CONCLUSION: Monitoring different grass species provided evidence for varying contribution in pollination across the main grass pollen season and highlighted the significance this impact may have on pollen allergy sufferers.