Report from AAAAI: Recent Findings in Peanut Immunotherapy
In our final report from the annual meeting of the American Academy of Allergy, Asthma & Immunology, we summarize some of the conference’s wide-ranging findings on peanut immunotherapy research, from the laboratory benchtop to clinical trials. The four studies below are among more than 100 talks, posters and sessions on peanut allergy presented at AAAAI 2017.
Results were reported for an open-label follow-up study of epicutaneous immunotherapy (EPIT) using Viaskin® peanut, a patch containing peanut protein that is worn on the skin and replaced daily. The 2014 VIPES study (Viaskin® Peanut’s Efficacy and Safety) – a 12-month double-blind placebo-controlled phase IIb clinical trial that enrolled 221 subjects – found that EPIT was most effective in children aged 6-11 years who were treated with the highest dose (250 micrograms peanut protein per patch). Of these subjects, more than half (15 of 28) were found to have responded to the treatment, passing a 1,000-mg oral food challenge or increasing by at least 10-fold their eliciting dose (the threshold dose at which they reacted). In the placebo group, about one in five children in this age range showed a comparable response to treatment.
By the end of the 24-month follow-up period, a higher fraction of young subjects – 15 of 18, or more than 80 percent – responded to the 250-μg patch, passing a 1000-mg OFC or showing at least a 10-fold increase in eliciting dose. The compliance rate was 95%. The dropout rate due to adverse events was 2.3 percent, and no serious adverse events were reported.
In sublingual immunotherapy (SLIT), the allergen is dissolved in a solution and administered under the patient’s tongue. Compared to oral immunotherapy (OIT), SLIT is typically associated with fewer gastrointestinal symptoms during treatment. Researchers at the University of North Carolina (UNC) investigated whether SLIT can result in sustained unresponsiveness, or desensitization that persists for some time after immunotherapy is discontinued.
Children ages 1 to 11 years were treated with peanut SLIT for three to five years in a clinical trial. Of the 37 patients who completed the study, 86 percent could tolerate more than 300 milligrams of peanut protein, and 32 percent (12 patients) passed a 5000-mg oral food challenge, eating about one-fifth of an ounce of peanut protein. When these 12 patients were re-challenged two to four weeks after SLIT was discontinued, ten passed the second 5000-mg challenge. Thus, about one-quarter of the individuals who completed the study remained unresponsive to peanut two to four weeks after stopping SLIT.
We anticipate reporting more about SLIT in the future, as FARE is funding a new clinical trial of peanut SLIT in young children that is currently being conducted at UNC and University of Texas Southwestern Medical Center.
At Children’s Hospital of Philadelphia, part of the FARE Clinical Network, a quality improvement project surveyed patients who had completed clinical trials for one of three peanut immunotherapy methods: oral immunotherapy (OIT), OIT combined with the IgE-binding drug Xolair® (omalizumab, O+OIT) and epicutaneous immunotherapy (EPIT).
Of 33 participants surveyed, all responded and reported being happy to have participated in their clinical trial. Most of the participants (27 of 33) included peanut in their diet, but about half reported that peanut dosing interfered with daily life. Measures of this interference were significantly lower for subjects who had completed EPIT than for subjects who had completed OIT. While some of the EPIT subjects liked the taste of peanut, none of the OIT or O + OIT subjects did.
The O + OIT group consumed the largest average dose, but also experienced the most serious adverse reactions. Of the four cases of epinephrine-treated anaphylaxis after immunotherapy, three occurred in the O + OIT group. (The fourth patient who required epinephrine was an adolescent who had not responded to EPIT and had subsequently been offered OIT.) Two participants – one each from the OIT and O + OIT groups – complained of gastrointestinal symptoms.
Substances that enhance immune response to an antigen are called adjuvants. Nano-scale emulsion – tiny droplets of oil, water and surfactant – can be used as an adjuvant in vaccines delivered as a nasal spray. Because the nano-emulsion promotes responses to antigen that involve IgG and IgA antibodies, research is being conducted at the University of Michigan to test whether nano-emulsion plus allergen might shift immune responses away from the production of allergy-associated IgE antibodies.
Several doses of an intranasal vaccine containing nano-emulsion plus peanut protein were used to immunize peanut-sensitized mice. Compared to non-immunized peanut-sensitized mice, the immunized mice had fewer IgE antibodies, lower levels of some allergy-associated proteins, and enhanced immune responses associated with fighting infections and tolerating antigens. When challenged with antigen, the immunized mice showed diminished symptoms of allergic hypersensitivity and anaphylaxis. Similar results were observed in egg-sensitized mice that were vaccinated with nano-emulsion plus egg protein. While this work is at a very early stage, these preliminary results are encouraging.
You can learn more about FARE-funded food allergy research here at the FARE Blog (click on the Research menu option above) or at foodallergy.org.
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