7 Current trends in AIT
Current trends in AIT seek novel routes of allergen administration as e.g. the use of allergens or allergoids formulated with adjuvant systems or native allergens displayed on virus-like particles (VLPs). Many of these novel approaches favour induction of IgG1 rather than IgG414. It could therefore be considered that allergoids either share some structural features with viral antigens as eg forming aggregates that present the epitopes in a more rigid and repetitive structures compared to native allergens. Ordered and repetitive surfaces are unique features of viral and bacterial surfaces and, hence, considered to be a pathogen-associated structural pattern (PASP)30.
Such considerations may offer insights into the surprisingly large treatment effect size in a recent exploratory field trial using a mixed Grass-SCIT-based allergoid combined with a novel adjuvant system (MCT®-MPL®) in the late stages of clinical development31. Approximately a 40% reduction of the Combined Symptom and Medication Score were achieved during the peak Grass Pollen Season (GPS) compared to placebo using a new regimen of only six pre-seasonal monthly injections31. In this study, grass-specific serum of IgG4 (n=37) and total IgG (n=10) was statistically significantly increased (LS mean ± SE: +3.34 mg/L ±0.946, p = .0006 and 79.94 mg/L ±111.10 (p = .0004)) at the start of the grass pollen season and remained elevated at the end of the grass pollen season.
It is worth noting that detection of specific IgG1 antibodies is not possible with the high throughput ImmunoCap Phadia platform used to support large-scale sampling from clinical trials. However, a grass specific (mix) IgG is commercially available and covers all subclasses including IgG1 and IgG4. Based on the fact that IgG1 makes up 60% of all IgG subclasses while IgG4 only 4%, measurement of grass specific total IgG will likely mainly represent changes in IgG1 levels.
Given recent developments in the field studying the importance of IgG subclasses and the classification of IgG1 as an equally dominant IgE-blocking antibody as IgG4, this will be a further potential biomarker correlate of the pivotal phase III trial, where specific IgG1 data is currently being collected for a sub-population-group of patients on active treatment. This will add further clinical evidence whether IgG1 and IgG4 subclass induction are equally important and both may constitute a hallmark of successful short-course pre-seasonal AIT; attributed to its adjuvant system (including a toll-like receptor 4 ligand) and nature of ligands (allergoid as opposed to native allergens) in the formulation.