Allergy Therapy by Intranasal Administration with Recombinant <i>Lactococcus lactis</i> Producing Bovine β-Lactoglobulin

Abstract

Background: In the last years, the use of probiotics such as lactic acid bacteria (LAB) has been proposed as an attractive alternative for the management of allergic diseases. A partial prevention from sensitization to bovine β-lactoglobulin (BLG), one of the major cows’ milk allergens, could be achieved in mice after intranasal administration with a recombinant LAB strain, Lactococcus lactis, producing BLG (LL-BLG). This study aimed to evaluate the effects of the LL-BLG strain in a therapeutic protocol. Methods: Three groups of mice were first orally sensitized to cows’ milk and then intranasally administered with either the LL-BLG strain, BLG protein alone or saline solution. Serum samples were collected to analyze BLG-specific IgE, IgG1 and IgG2a, and mice were further intranasally challenged with BLG to elicit a specific allergic reaction. Results: Treatment with LL-BLG, but not with BLG alone, contributed to diminish IgG1 production in serum and bronchoalveolar lavage fluids. This was associated with decreased IL-4 production and enhanced IFN-γ production by BLG-reactivated splenocytes, suggesting a switch from Th2- to Th1-immune response. Furthermore, we observed that administration of LL-BLG or LL locally reduced the allergic reaction induced after intranasal challenge, as evidenced by decreased release of IL-4 in bronchoalveolar lavage fluids. Conclusion: These preliminary results demonstrate the efficiency of the intranasal administration of LL-BLG for specific therapy against cows’ milk-related allergy.

Recombinant Lactococcus lactis can make the difference in antigen-specific immune tolerance induction, the Type 1 Diabetes case

“…Broncheoalveolar lavages show reduced IL-5 and reduced number of eosinophils, while, both in the airways as well as in the gut, specific IgA was increased [77]. Intranasal inoculation of L. lactis producing BLG post sensitization reduced mucosal as well as systemic IgG1 and showed diversion of splenocytes towards Th1 [78]. Taken together, these reports propose the induction of IgA and the avoidance of Th2 response as prominent endpoints and show that - at least to a certain extent - these can be met by use of recombinant L. lactis .…”

“…To provoke responses, these molecules interact with pattern recognition receptors of the host [83]. A number of reports show that also L. lactis strains can exert similar immune modulatory effects [78,84-86], amongst others driven by teichoic acids [87], also in conjunction with purified allergen [88]. Again, this shows that L. lactis in itself is a good candidate delivery vehicle.…”

Future therapies for food allergies

“…There was also decreased IL-4 production and enhanced IFN-γ production by β-lactoglobulin-stimulated splenocytes, indicating a switch from Th2-to Th1-immune response. 92…”

Vaccines and Immunomodulatory Therapies for Food Allergy

“…Treatment with L. lactis-IL-10 prior to sensitization led to decreased anaphylaxis scores on challenge, and intranasal treatment with L. lactis-IL-12-β-lactoglobulin after sensitization led to decreased allergic response on intranasal challenge of β-lactoglobulin [51,52].…”