TABLE 2.

The comparison of native, recombinant, and engineered recombinant allergen immunotherapy (IT) for food allergy

Therapy	Mechanism of Action	Effects	Comments
Conventional peanut IT	Altered T-cell responses, up- regulation of suppressor cells in allergen IT	Increased oral peanut tolerance	Subcutaneous injections of gradually increasing doses of allergen, unacceptably high rate of serious adverse events
Birch pollen IT for oral allergy to apple	Marked reduction in skin test to raw apple; IT inversely correlated with baseline skin test but not with serum apple or birch-IgE	Significant reduction or total resolution of oral allergy to raw Golden Delicious apple in a subset of patients receiving IT for at least 12 months	Clinical effect lasting for up to 30 months after discontinuation in >50% of patients
Oral desensitization	Presumed oral tolerance induction; decreased skin test reactivity, increased serum food-IgG/IgG4, no change in food-IgE, increased food-specific CD4+CD23high T cells, increased IL-10 on food antigen stimulation	Tolerance to regular servings of food in most subjects (70–80%) maintained as long as food ingested on regular basis for up to 6 months; in a subset increased threshold dose for clinical reactions	Up to 50% experience systemic side effects; some patients require uninterrupted ingestion of food to maintain desensitized tolerant state; rigorous clinical trials necessary to determine safety and efficacy
Sublingual IT with hazelnut extract	Presumed oral tolerance induction; increased serum hazelnut-IgG4 and total IL-10 level, no change in hazelnut-IgE	Increased oral hazelnut tolerance	Systemic reactions in only 0.2% of doses during build up phase, treated with oral antihistamines; rigorous clinical trials necessary to determine safety and efficacy
Plasmid DNA- based IT	Induces prolonged humoral and cellular responses due to CpG motifs in the DNA backbone	Protection against peanut anaphylaxis in sensitized AKR/J mice, but induction of anaphylaxis in C3H/HeJ (H-2K) mice; no effect on peanut-IgE antibody levels	Serious concerns regarding safety in view of strain- dependent effects in mice, concern for excessive Th 1 stimulation and autoimmunity
Immunostimulatory sequences (ISS- ODN)	Potent stimulation of Th 1 via activation of antigen- presenting cells, natural killer cells, and B cells; increased Th 1 cytokines	Protection against peanut sensitization in mice	Not shown to reverse established peanut allergy, concern for excessive Th 1 stimulation, and potential for autoimmunity
Engineered recombinant peanut IT	Binding to mast cells eliminated, T-cell responses comparable to native peanut allergens	Protection against peanut anaphylaxis in mice	Improved safety profile compared with conventional IT, requires identification of IgE binding sites
Heat-killed bacteria mixed with or expressing engineered recombinant peanut proteins	Potentiation of Th 1 and T- regulatory cytokine responses	Protection against peanut anaphylaxis in mice, lasting up to 10 weeks after treatment	Concern for toxicity of bacterial adjuvants, excessive Th 1 stimulation, and potential for autoimmunity; heat-killed E. coli expressing modified peanut allergens administered rectally viewed as the safest approach for future human studies