Preventive immunotherapy of peanut allergy: the impact of dose and route of administration

Background: Allergen immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy (PA). However, route of administration and dose of allergen may influence efficacy and safety of IT for PA. Understanding the impact of dose and route of administration would help ensure more efficient strategies for preventive IT of PA, and thus ensure the lives of those at risk of developing PA. In this study, we compared peanut allergen delivery via oral cavity, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes of administration in a dose- response manner, as well as the ability of each route of administration to prevent sensitization and PA development in Brown Norway (BN) rats. Method: BN rats were exposed to peanut protein extract (PPE) via the oral cavity (1 mg, 10 mg or 100 mg, daily), SL (10 μg, 100 μg or 1000 μg, daily), IG (1 mg, 10 mg or 100 mg, daily), or SC (1 μg, 10 μg or 100 μg, 3 times/week) route of administration for three weeks. Hereafter the animals were post- immunized via weekly intraperitoneal (IP) injections for four weeks. Lastly, the animals were challenged with PPE via an ear swelling test, as well as an IP and an IG challenge for detection of symptoms and body hypothermia. Sera were analyzed by ELISAs and spleens were stimulated with PPE for analysis of humoral and antigen- specific cellular responses, respectively. Results: All doses administered via IG and SL routes of administration as well as the high dose of oral cavity administration did not induce PPE sensitization prior to the post- immunization regimen. In contrast, all doses administered SC induced PPE sensitization, indicating that safety was dependent on both dose and routes of administration. A dose- response pattern emerged upon IP post- immunizations with PPE for IG, SL and oral cavity administration, indicating that the greater the dose, the greater the preventive capacity for PPE sensitization. Proliferative responses of spleenocytes supported the dose- dependent preventive immunotherapeutic capacity of IG, SL and oral cavity routes of administration. Conclusion: PPE administered IG, SL and orally promoted prevention of PA, whereas SC administration promoted peanut sensitization. Highest dose administered IG or orally showed superiority in preventing PA by withstanding IP and IG challenges. These differences may be important to consider when choosing a route of administration in preventive allergen IT.