The addition of CpG to alum-adjuvanted vaccines provides a bystander effect that reduces the severity of peanut allergy in mice. (HYP7P.311)

Abstract

Abstract Rationale: The “hygiene hypothesis” predicts that a “clean” environment increases the risk of developing allergic disease while endotoxin exposure is protective. The vaccine adjuvant alum may alter immune responses to enhance the induction or severity of allergic disease. A mouse model of peanut allergy was utilized to determine if endotoxin or alum exposure influence the severity of allergic disease. Methods: C3H/HeN mice were housed in high or low endotoxin environments. Mice received three biweekly ovalbumin (Ova) immunizations adjuvanted with alum or alum combined with MPL or CpG 1826. Peanut sensitization was achieved by gastric gavage of peanut and cholera toxin weekly for 4 weeks beginning one day after immunization with Ova + adjuvants. One week after the last immunization all mice were challenged with peanut and monitored for hypothermia and allergy clinical symptoms. Results: Mice immunized with Ova + Alum + CpG exhibited mild allergic symptoms after peanut challenge (-2.0°C and 1.8 score) that did not statistically differ from challenged unsensitized mice (0.68°C and 0 score). All other immunization groups exhibited severe allergic symptoms after challenge (< -2.5°C and >2.5 score) and were significantly different when compared to challenged unsensitized mice. Conclusion: Endotoxin and alum exposure did not increase the severity of peanut allergy. The addition of CpG 1826 to the Ova + Alum vaccine reduced the severity of peanut-specific allergic disease.