Mouse strain differences in response to oral immunotherapy for peanut allergy

Abstract

Background Promising therapies for food allergy are emerging, mostly based on animal experimentation. However, different mouse strains are used, which may make it hard to compare experiments. The current study investigated whether the immunological differences between C3H/HeOuJ (C3H) and BALB/c mice lead to differences in efficacy of peanut‐specific immunotherapy. Methods After sensitization using peanut extract (PE), C3H and BALB/c mice received oral immunotherapy (OIT) by intragastric dosing for three weeks. Hereafter, mice were exposed to PE via the intradermal, intragastric and intraperitoneal route, to determine allergic outcomes. Furthermore, PE‐specific antibody and cytokine production were determined and the number of various immune cells at different time points during the study were measured. Results OIT protected C3H mice against anaphylaxis, whereas no anaphylaxis was seen in BALB/c mice. In contrast, OIT induced an increase in MMCP‐1 levels in BALB/c mice but not in C3H mice. No effect of OIT on the acute allergic skin response was observed in either strain. Specific antibody responses showed similar patterns in both strains for IgA and IgG1. IgE levels were a tenfold higher in BALB/c mice and after the intragastric challenge (day 70) OIT‐treated BALB/c mice showed induced IgE levels. Moreover, in C3H mice IgG2a levels were higher and increased in response to OIT and challenges. After the final challenge, but not at other timepoints MLN‐derived lymphocytes from OIT‐treated BALB/c mice produced less IL‐13 and IL‐5 compared to control‐treated mice, whereas no differences were seen in case of C3H mice. Conclusions Taken together, these results show that the C3H strain is more suitable to study clinical outcomes of OIT, whereas the BALB/c strain is more optimal to study T cell responses.

Allergen-Specific IgA Antibodies Block IgE-Mediated Activation of Mast Cells and Basophils

“…We initially found marked increases in allergen-specific IgA in a trial of OIT for peanut an observation that has subsequently been extended by others to cow's milk and egg OIT (14,(32)(33)(34)(35). Murine models have also documented specific IgA responses following food allergen ingestion and OIT (24,(36)(37)(38). Despite the consistent observation of association between IgA responses and food tolerance in humans and in murine models of food allergy, neither the direct contributions of IgA to tolerance nor the mechanisms thereof have been established.…”

A Comprehensive Review on Natural Bioactive Compounds and Probiotics as Potential Therapeutics in Food Allergy Treatment

“…In general, mouse models that are currently being used for inducing food allergy have some intrinsic limitations. Presently, mouse models of food allergy are developed with the help of adjuvants (e.g., alum, freund's complete adjuvant and cholera toxin B) in genetically distinct mouse strains (e.g., Balb/c or C3H/HeOuJ) using different routes of sensitization (e.g., intraperitoneal and intragastric) ( 173 – 175 ). Hence, most studies reporting the efficacy in murine systems tend to fail or show no efficacy when replicated in clinical studies ( 106 ).…”

Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy

“…The BLG-p(Man) treatment substantially increased the BLG-specific IgG levels, which outcompeted the increase in IgE, resulting in a reduced IgE/IgG ratio (Figure 5E-G). Interesting, we also observed that the BLGp(Man) treatment significantly induced BLG-specific IgG2a production, an Th1-biased IgG subtype that can be particularly protective against Th2-biased allergic responses in mice 50,52,54,56 . This suggests a specific Th2 suppression mechanism induced by BLG-p(Man) therapy, which was further supported by several in vitro antigen restimulation cytokine analyses (Figure 4D, E; Figure S4G, S7D, E, and S8 F,H).…”

“…This can be beneficial in neutralizing allergens, as well as blocking IgE-mediated responses by binding to mast cells and basophils 49 . In C3H mice, IgG2a — a Th1-biased antibody subtype — stands out for its higher increase to various immunotherapies 50, 52, 54, 56 , potentially through the suppression of Th2-driven allergic responses. We further investigate the changes in BLG-specific IgG2a and IgG1 subtypes in response to BLG-p(Man) therapy in allergic mice.…”