Table 1.

Preclinical models of food allergy immunotherapy.

Immunotherapy route	Food allergy model	Immunotherapy schedule	Allergen dose	Formulation	Allergic response outcome	Ref
Oral immunotherapy
	Peanut	5x/week for 3 weeks	15 mg	PBS	•Decrease hypothermia in C3H mice •Increase mmcp1 in BALB/c mice •Decrease MLN IL-13 and IL-5 in BALB/c mice	(22)
	Egg (ovomucoid, OM)	Daily for 10 days	0.5–5 mg	Water	•Increase vascular permeability •Increase serum IgG1 and IgE •Increase ConA-stimulated IL-4 and IL-5 •Decrease ConA-stimulated IL-10 and IFNγ	(24)
	Egg white (EW)	Daily for 10 days	1–16 mg	Saline	•Decrease egg white-specific IFNγ •Increase OM-specific plasma IgE •Increase EW and OM-specific IgA	(25)
	Peanut	Daily for 8 weeks	1–5 mg	PBS	•Decrease serum IgE •Increase serum IgG2a •Decrease peanut-specific IL-5 and IL-13 •Increase peanut-specific IL-10 •Increase Foxp3+ T cells	(26)
	Egg ovomucoid (OM)	Continuous feeding for 4 weeks	1% OM	Mouse chow containing 19% casein + 1% OM	•Reduced allergy symptoms after an oral challenge •Reduced vascular permeability •Increase plasma OM-specific IgA	(27)
	Egg white	Continuous feeding for 4 weeks	0.01%, 0.1%, or 1% EW	Mouse chow containing casein	•1% EW reduced diarrhea incidence •Increase OM-specific IgE and IgA after 2 weeks of therapy but decrease IgE and IgA at the end of the study •Increase EW-specific IFNγ, IL-10 and Foxp3+ T cells	(28)
	Buckwheat	Continuous feeding for 6 weeks	0.03% phosphorylated or unphosphorylated antigen in mouse feed	Mouse chow	•Phosphorylated antigen reduced allergic symptom score •Decreased total and allergen-specific serum IgE •Increased total and allergen-specific serum IgA •Increased Tfh cells in Peyer's patches	(29)
	Egg white	3x/week for 3 weeks	5 mg of digested protein	In PBS	•Induce DCs to suppress T cell IL-5, IFNγ, and IL-17 in coculture systems •Induce DCs and T cell cocultures to increase TGFβ and Foxp3+ RORγt+ cell populations	(30)
	Egg ovomucoid	Daily for 2 weeks	1–50 mg	Lactobacillus casei rhamnosus (1 × 109 CFU per day)	•Prevented allergen-induced hypothermia •Decreased allergy symptom score •Decreased serum IgE, IgA, IgG1, and IgG2a compared to OIT alone •Reduced goblet cell numbers in the small intestines	(31)
	Peanut	Once a week for 4 weeks	200 μg	In PLGA nanoparticles +CpG (1.8 μg)	•Reduced allergen-induced hypothermia •Decreased allergic symptom scores •Decrease plasma histamine •Decrease serum peanut-specific IgE and IgG1 •Increase serum peanut-specific IgG2a •Decrease peanut-specific IL-4, IL-5, and IL-13 •Increase peanut-specific IFNγ	(32)
	Peanut	5x/week for 3 weeks	1.5 or 15 mg	OIT in PBS while continuously feeding a diet containing 1% short and long-chain fatty acid fructooligosaccharide prebiotics	•High dose OIT reduces hypothermia in the presence and absence of prebiotics •Low dose OIT reduces hypothermia in the presence of prebiotics	(33)
	Cow milk	5x/week for 3 weeks	10 mg	OIT in PBS supplemented with 0.6 g/kg bodyweight per day of sodium butyrate	•Suppresses mast cell activation and mast cell IL-13 and IL-6 production •Reduce allergic symptoms after intragastric and intradermal challenge •Decrease allergen-specific serum IgE	(34)
Sublingual immunotherapy
	Peach	Once a week for 8 weeks	1 nmol	With CpG (50 μg) in PBS	•Decrease hypothermia •Decrease serum IgG1 and IgE •Increase Tregs •Decrease CD4+IL-4+ cells •Increase CD4+IFNγ+ and CD4+IL-10+ cells	(23)
	Peanut	Once a week for 8 weeks	100 μg	1.2% carboxymethylcellulose	•Decrease serum IgE •Increase serum IgG2a •Decrease peanut-specific IL-5 and IL-13 •Increase peanut-specific IL-10 •Increase Foxp3+ T cells	(26)
	Cow milk	Twice a week for 8 weeks	10 pg–10 ng	Omp16 (50 μg)	•Reduced allergy clinical symptom score and foot pad inflammation compared to SLIT alone •Increase antigen-specific IgG2a •Decrease serum IgG1:IgG2a ratio •Decrease antigen-specific IL-5 and IL-13 •Increase antigen-specific IFNγ •Increase IFNγ+ cells in both CD4+ and CD8+ cells that transfer protection to other hypersensitive mice	(35)
	Peach	Once a week for 8 weeks	1, 2, or 5 nmol	PBS	•2 nmol dose prevented allergen-induced hypothermia 1 and 5-weeks post-therapy •Decrease CD4+IL-4+ cells •Increase CD4+IFNγ+ cells •Increase in Tregs and CD4+IL-10+ cells	(36)
Epicutaneous immunotherapy
	Cashew	48-h patch every week for 8, 12, or 16 weeks	50 μg	Phosphate buffer	•Decrease allergy symptoms and hypothermia after 16-week therapy •Reduce mmcp1 after 8-week therapy •Reduce IgE and IgG1 after 16-week therapy •Increase IgG2a	(21)
	Peanut	48-h patch every week for 8 weeks			•Decrease serum IgE •Increase serum IgG2a •Decrease peanut-specific IL-5 and IL-13 •Increase Foxp3+ T cells •Increase Foxp3+ T cells from naïve population •Maintain enhanced Treg population 8 weeks post-therapy	(26)
	Peanut	Weekly for 5 weeks	∼11.3 μg for microneedles 100 μg for EPIT patch	Microneedles with a 5-min exposure time EPIT patch with 24-h exposure time	•Microneedles reduced allergy symptom score and serum mmcp1 levels •Microneedles prevented allergen-induced hypothermia •Microneedles decreased antigen-specific IL-4, IL-5 and IL-21 in the spleen and MLN •Microneedles increased antigen-specific IFNγ in the spleen and MLN •Microneedles increased antigen-specific IL-10 in the MLN. Microneedles enhance serum IgG2a and IgG2b and decrease serum IgE compared to EPIT	(37)
Nasal Immunotherapy
	Peanut	3x/week for 4 weeks	40 μg	CpG (20 μg) in saline	•Decreased allergic symptoms and hypothermia, Decrease IL-5 and IL-13 •Increase IL-10 and IFNγ •Increase serum IgG2c and mucosal IgA	(15)
	Cow milk	Every 4 weeks for 16 weeks	20 μg	20% Nanoemulsion	•Reduced allergen-induced hypothermia, clinical symptom scores and serum mmcp1 4 and 16 weeks post-therapy •Decreased IL-4 and IL-13 and increased IFNγ,IL-10, IL-17, and IL-22 4-weeks after therapy. •Further enhanced immune responses compared to nasal therapy with antigen alone 16 weeks post-therapy •Decreased serum IgE and IgG1 and increased serum IgG2a	(38)
	Peanut	Every 4 weeks for 12 weeks	20 μg	20% Nanoemulsion	•Decrease antigen-specific serum IgE and IgG1 •Increase antigen-specific serum IgG2a and IgG2b, mucosal IgA •Decrease antigen-specific IL-4 and IL-13 •Increase antigen-specific IFNγ, IL-17, IL-10, and IL-2 •Reduce allergic symptom score and antigen-induced serum mmcp1	(39)