BACKGROUND:Oral immunotherapy, if proven safe and effective, could be an alternative to subcutaneous immunotherapy. OBJECTIVE:This pilot study investigated the clinic and immunologic effects of ragweed immunotherapy using a new microencapsulated, pH-sensitive, oral delivery system. METHODS:A double-blind, placebo-controlled trial was conducted in 23 patients with allergic rhinitis to short ragweed. Following a baseline nasal challenge with ragweed allergen, oral immunotherapy with encapsulated short ragweed extract or placebo was administered once daily, 6 days/week. Dosed began at 3 micrograms Amb a 1 per day and were increased by 3 micrograms every three days as tolerated, to a maximum daily maintenance dose of 24 micrograms. A nasal challenge was repeated 6 weeks, later, followed by the continuation of maintenance therapy through the natural ragweed season. Daily allergy symptoms and relief medication usage was recorded. A final nasal challenge was performed at the end of the natural season. Short ragweed-specific serum IgE, IgG, and IgG4 antibody levels were measured every 2 weeks during the study. RESULTS:Maximum tolerated doses ranged from 6 to 24 micrograms Amb a 1 per day (74% reached 24 micrograms). Adverse events were not serious or different between the active and placebo groups. The active group showed increased in short ragweed-specific serum IgG and IgG4 antibody levels. Symptom scores during the natural season were numerically but not statistically lower in the active treatment group. This group also experienced a greater reduction from baseline in nasal reactivity as assessed by nasal challenge. CONCLUSIONS:These pilot data suggest that the encapsulated, pH-sensitive oral immunotherapy delivery system was safe, induced a brisk serologic response, and attenuated the symptomatic response to both experimental and environmental ragweed exposure.