Oral immunotherapy with betalactoglobulin peptides can reduce allergic symptoms in a mouse model for cow's milk allergy

Background: Several studies investigated the potential of oral immunotherapy for cow's milk allergy. Because this therapy was associated with significant side effects, it is still not used in the clinic. Our hypothesis is that by using peptides instead of proteins these side effects may be reduced. In this study the potential of oral immunotherapy with synthetic beta-lactoglobulin peptides was investigated in a mouse model for cow's milk allergy and compared to whey and partial whey hydrolysates. Method: Female C3H/HeOuJ mice were sensitized five times by oral gavage with whey. Five days after the last sensitization, blood was withdrawn and IgE was measured to determine sensitization. One week later, treatment was started. Mice were orally treated 14 times during four weeks with PBS, whey, partial whey hydrolysates or a peptide-mix. Two doses of whey and partial hydrolysates were tested. Three days after the last treatment, an intradermal ear and oral challenge were performed. The mice were sacrificed the following day. Result: In all mice IgE for whey was detected after sensitization. Treatment with the peptide mixture could significantly reduce the acute allergic ear response compared to the PBS-treated mice. Also the partial hydrolysates and the low dose of whey showed a reduction. Interestingly, the high dose of whey showed no effect. This group showed also increased antibody levels compared to the PBS-treated group. The peptide-treated mice showed no difference in IgE and IgG2a levels compared to the control group. Instead, the IgG1 levels were higher in the mice treated with peptides compared to the PBS-treated mice. Conclusion: Oral immunotherapy with a mixture of synthetic beta-lactoglobulin peptides could reduce the acute allergic symptoms in mouse model for cow's milk allergy. This therapy seems more efficient than the conventional immunotherapy with whey. Further investigation is necessary to determine the mechanism of action.