House dust mite allergy and treatments

The prevalence of allergic asthma, the most common allergic disease, increased dramatically in the last 20 years. This exacerbated immune-mediated disorder is characterized by chronic airway inflammation, mucus production, and variable airflow obstruction with airways hyperresponsiveness (AHR). House dust mites (HDM) can be considered as one of the most important provider of inhalant allergens within the world and the mite sensitization affects more than 20% of the population from industrialized countries, including Thailand.
As it is clearly established that allergen-specific Th2 cells play the central role for the mediation of this chronic inflammatory response, the aim of a vaccine against HDM allergy could be the induction of allergen-specific Th1 or Treg cells to prevent or to skew the Th2 response into a protective one. 

Conventional allergen-specific immunotherapy (SIT) is, up to now, the unique immune-modifying therapy that has been recommended for the specific treatment of HDM allergy. When effective, such immunotherapy triggers Th1 or Treg cytokines (IFNg, IL-10, TGFb) as well as blocking allergen-specific IgG4 antibodies to down-regulate the Th2-biased allergic response. However, such treatment presents some disadvantages and is sometimes risky. Indeed, SIT involves 50-80 subcutaneous (SCIT) or sublingual (SLIT) administration of HDM allergen extracts using incremental regimes within 1 to 3 years. The other main limiting factor in SIT is anaphylactic side-effects, which vary in incidence from 0.1-5% of individuals (prime/boosting of specific IgE response by using natural allergen displaying IgE reactivity) and the triggering of new allergic responses against allergens for which patients were not sensitized prior to these treatments. Moreover, there are issues about the production, standardization and composition of the HDM allergen extracts. Notably, it is well known that some important HDM allergens are present in very tiny amounts in such allergen extracts.

Because of these above disadvantages, innovative and more effective therapies are urgently required. Thanks to the great advances in molecular allergology and immunology, new anti-allergy vaccines are currently developed to treat HDM allergy and asthma.

House Dust Mite Vaccine

Since it was postulated that DNA immunization could preferentially induce Th1 responses and also, as demonstrated recently, tolerance, we developed DNA vaccines encoding major HDM allergens. Highly purified endotoxin-free DNA preparation can be easily obtained with reproducibility and at low cost. DNA vaccines are moreover highly stable and consequently do not need cold chain for their storage. Following DNA vaccine administration, the expressed allergen by transfected cells can be taken up by antigen presenting cells (DCs mainly) to elicit potent Th1-biased allergen specific response. 

We clearly demonstrated that vaccinations with a DNA plasmid encoding the major HDM allergen Der p 2 and delivered in-vivo by electroporation prevent the development of HDM allergy in mice. We currently evaluate therapeutic vaccinations in pre-sensitized animals. As, it is well accepted that heterologous prime–boost is more effective than the ‘homologous’ prime–boost approach, we will also combine recombinant Der p 2 protein with specific pro-Th1 adjuvants in such vaccination protocols. 

We believe that the consistent preclinical results generated from this research will allow to conduct rapidly clinical trials.

Immunol Lett. 2013 Mar;151(1-2):23-30

Efficacy of prophylactic DNA vaccinations using different prime-boost regimens

Selected Publications

The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity. Int Arch Allergy Immunol. 2016;168(3):150-60.

The minor house dust mite allergen Der p 13 is a fatty acid-binding protein and an activator of a TLR2-mediated innate immune response. Allergy. 2016 Oct; 71:1425-34.

Patterns of IgE sensitization in house dust mite-allergic patients: implications for allergen immunotherapy. Allergy. 2016 Feb;71(2):220-9.

Development of recombinant stable house dust mite allergen Der p 3 molecules for component-resolved diagnosis and specific immunotherapy. Clin Exp Allergy. 2015 Apr;45(4):823-34.

Characterization of the house dust mite allergen Der p 21 produced in Pichia pastoris. Protein Expr Purif. 2014 Sep; 101:8-13.

Orchestration of an uncommon maturation cascade of the house dust mite protease allergen quartet. Front Immunol. 2014 Mar 31; 5:138.

Is electroporation decisive for the efficacy of DNA vaccine against house dust mite allergy? Expert Rev Vaccines. 2013 Sep;12(9):977-9.

Innate immune responses in house dust mite allergy. ISRN Allergy. 2013 Feb 28; 2013:735031.

Optimization of a Der p 2-based prophylactic DNA vaccine against house dust mite allergy. Immunol Lett. 2013 Mar;151(1-2):23-30.

Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation. Clin Exp Allergy. 2011 Dec;41(12):1784-92.