Research Projects

Dust mites (DM) allergens are major triggers of IgE-mediated atopic asthma. In India, more than 50% of atopic asthma attacks are caused by inhalant dust mite allergens. Currently in India, allergy diagnosis is based on skin prick tests or IgE-serology using crude DM extract which are mostly unstandardised and frequently give false positive or false negative results. Recombinant allergen based multiplex-assay system is the state-of-the-art technique for allergy diagnosis in Western countries. In addition to diagnosis, the major pitfall in the clinical management of DM-related asthma includes the recurrent use of corticosteroids, anti-histamines and other symptomatic drugs that cannot cure the root cause of the disease and can lead to severe side effects upon long-term use. On the contrary, SIT has been proven as a more targeted and disease-modifying approach with long lasting effects. The present proposal aims to investigate the major allergenic molecules of DM which will facilitate the design component-resolved diagnostics customised for the Indian population. Here, we will target 5 major groups of cross-reactive allergens of DM that have already shown high frequency of sero-reactivity in earlier studies done with other populations such as Caucasian, Hispanics, and Asians. In addition to IgE-binding capacity, the clinical relevance of these 5 allergens will be evaluated by basophil activation test. Our next plan is to design vaccine candidates using peptides that can mount blocking IgG-antibodies specifically directed towards the IgE-epitopes of the allergens. These peptides will be derived from the allergen sequences but will be confirmed to lack IgE-binding (i.e, hypoallergenic) and allergen-specific T-cell reactivity in order to avoid anaphylaxis and delayed hypersensitivity respectively. These peptides will be used as haptens and will be fused in various combinations with a carrier immunogen for T-cell help. A number of such constructs will be designed against each allergen group and will be assessed to induce tolerance by mounting protective antibody (IgG) response and skewing Th2 phenotypes into Th1. A vaccine construct showing optimum immunotherapeutic potential against native DM allergen will be selected for encapsulation within PLGA nanoparticles. Physico-chemical properties and release kinetics of the encapsulated nano-vaccine will be studied by employing biophysical methods. The vaccination potential of the nano-encapsulated immunogen will be assessed in a mouse model of dust mite allergy. The encapsulation is expected to result in sustained release of immunogen as well as in enhanced level of stability, immunogenicity, adjuvenecity, and immune recognition to the vaccine molecule.