In:
Clinical & Experimental Allergy, Wiley, Vol. 41, No. 12 ( 2011-12), p. 1784-1792
Abstract:
Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. Objective To develop a chronic house dust mite ( HDM ) allergy model to evaluate sublingual therapeutic vaccine candidates. Methods The BABL /c mice that were used were sensitized with D ermatophagoides pteronyssinus ( D pte) and D ermatophagoides farinae ( D far) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy ( SLIT ) with either D pte, D far or D pte/ D far extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho‐alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. Results Mice sensitized to D pte and D far allergens exhibited strong airway hyperresponsiveness ( AHR ) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted T h2‐biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts‐based vaccines. In this model, SLIT decreased AHR and T h2 responses and induced HDM ‐specific I g A s in saliva. The D pte/ D far mix proved the most efficacious when compared to D pte or D far extracts alone. Conclusions and Clinical Relevance The efficacy of a sublingual vaccine based on a D pte/ D far allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans.
Type of Medium:
Online Resource
ISSN:
0954-7894
,
1365-2222
DOI:
10.1111/cea.2011.41.issue-12
DOI:
10.1111/j.1365-2222.2011.03865.x
Language:
English
Publisher:
Wiley
Publication Date:
2011
detail.hit.zdb_id:
2186232-1
detail.hit.zdb_id:
2004469-0
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