Allergen ISS conjugates in ragweed-induced asthma

Principal Investigator:
David H. Broide, University of California San Diego

Abstract | Investigators | News | Background | Resources

Basis/Rationale: Pre-clinical studies in mice demonstrate that AIC inhibits ragweed induced airway inflammation and airway hyperrreactivity in a mouse model of asthma. Several studies have demonstrated the safety of AIC administration in humans with allergic rhinitis. An ITN supported study at Johns Hopkins demonstrated that AIC significantly reduced rhinitis symptom scores during the ragweed season for two seasons following administration of one course of AIC, suggesting that AIC had long lasting immunomodulatory effects. Studies in subjects with ragweed induced asthma provide an opportunity to determine whether higher doses of AIC will be of benefit in providing long term reductions in asthma symptoms during the ragweed season, as well as an opportunity to study immunological T cell responses in the lower airway using induced sputum (in all subjects), as well as bronchoalveolar lavage, and endobronchial biopsy specimens (in a subset of subjects).

Significance: If AIC were able to induce tolerance to ragweed in subjects with seasonal increases in asthma symptoms, the methods used to develop AIC (e.g. conjugate an immunostimulatory sequence of DNA to a ragweed protein) could be applied to other allergens (cat, dust mite, grass pollen, etc) which contribute to asthma in a large number of individuals.

Relevance to immune tolerance: If one series of 6 weekly injections of AIC is able to induce long term (several years) tolerance to ragweed, such a therapy would be relevant to identifying novel therapies that induce immune tolerance in asthma.

Protocol Summary: We will recruit 60 ragweed allergic subjects who have co-existent ragweed-induced seasonal increases in asthma symptoms (documented in an observational year in this study), and determine in a randomized, double-blind, study design whether immunization with AIC after an observational year induces long term tolerance to ragweed as assessed by reductions in seasonal increases in symptoms of asthma (primary clinical outcome measure), and airway hyperreactivity (AHR) to methacholine. Immunological studies on sputum, BAL, and endobronchial biopsy will provide insight into potential mechanisms of tolerance induction.

Participating Investigators

	David H. Broide, University of California San Diego
	Peter Creticos, Johns Hopkins Asthma & Allergy Ctr
	Eyal Raz, University of California San Diego
	Mark Liu, Johns Hopkins University
	John Schroeder, Johns Hopkins University

News & Recent Developments

	New Positive Data from Phase II ITN Study of Ragweed Immunotherapy Product (AIC) [open]
	Dynavax, Johns Hopkins University and NIH-Sponsored Immune Tolerance Network Present New Positive Data from Phase II Study of Ragweed Immunotherapy Product (AIC) - DynaVax [go]

Background Articles

	ISS oligodeoxynucleotide-based vaccination and immunomodulation - J Allergy Clin Immunol [Abstract]
	Immunostimulatory DNA and applications to allergic disease - J Allergy Clin Immunol [go]
	Immunostimulatory DNA Sequences Inhibit IL-5, Eosinophilic Inflammation, and Airway Hyperresponsiveness in Mice - J Immunol [go]
	DNA-based immunization for asthma [Abstract]

Resources & Interesting Links

Dynavax Technologies ISS overview [go]