BACKGROUND For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. METHODS In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. RESULTS After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. CONCLUSIONS These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.)

Background-Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.

Background-Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.

Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness following withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at two U.S. centers. Subjects aged 1–16 were recruited and treated for up to five years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg peanut protein/day. Blood was collected at multiple time points. Clinical endpoints were measured with 5000 mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. 12/24 (50%) successfully passed a challenge one month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin tests as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2, and lower ratios of peanut-specific:total IgE, compared to subjects not passing. There were no differences in peanut IgG4 levels or functional activity at end-of-study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated up to five years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin tests and lower allergen-specific IgE levels were predictive of successful outcome.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the world. In women, genital infection can cause endometritis and pelvic inflammatory disease with the severe sequelae of ectopic pregnancy or infertility. Chlamydia sp. do not damage tissues directly, but induce an injurious host inflammatory response at the infected site. In the murine model of genital disease with Chlamydia muridarum, TLR2 plays a role in both early production of inflammatory mediators and development of chronic oviduct pathology. We report the results of studies with plasmid-cured C. muridarum mutants that retain the ability to infect the murine genital tract, but fail to cause disease in the oviduct. These mutants do not stimulate TLR2-dependent cytokine production in mice, nor in innate immune cells or epithelial cells in vitro. They induce an effective Th1 immune response, with no evidence for Th1-immune-mediated collateral tissue damage. Furthermore, mice previously infected with the plasmid-deficient strains are protected against oviduct disease upon challenge with virulent C. muridarum. If plasmid-cured derivatives of human C. trachomatis biovars exhibit similar phenotypic characteristics, they have the potential to serve as vaccines to prevent human disease.

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Background There are presently no available therapeutic options for peanut-allergic patients. Objective To investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). Methods After a baseline oral food challenge (OFC) of up to 2g of peanut powder (~50% protein) (median successfully consumed dose [SCD] 46mg), 40 subjects, aged 12–37 (median 15) years, were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5g OFC was performed after 44 weeks followed by unblinding; placebo subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5g OFC. Week 44 OFCs from both groups were compared to baseline OFCs; subjects successfully consuming 5g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results After 44 weeks of SLIT, 14/20 (70%) subjects receiving peanut SLIT were responders compared to 3/20 (15%) subjects receiving placebo (p<0.001). In peanut-SLIT responders, median SCD increased from 3.5mg to 496mg. After 68 weeks of SLIT, median SCD significantly increased to 996mg (compared to week 44, p=0.05). The median SCD at the Week 44 crossover OFC was significantly higher than baseline (603mg vs 71mg; p=0.02). 7/16 (44%) crossover subjects were responders; median SCD increased from 21mg to 496mg among responders. Of 10,855 peanut doses through Week 44 OFCs, 63.1% were symptom-free; excluding oral/pharyngeal symptoms, 95.2% were symptom-free. Conclusions Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared to placebo. Longer duration of therapy showed statistically significant increases in the SCD.

Background Oral immunotherapy offers a promising therapeutic option for peanut allergy. Given that during oral immunotherapy an allergic patient ingests an allergen that could potentially cause a serious reaction, safety of oral immunotherapy is of particular concern. Objective The purpose of this study is to examine safety during the initial escalation day, build-up phase, and home dosing phase in subjects enrolled in a peanut oral immunotherapy study. Methods Skin, upper respiratory, chest and abdominal symptoms were recorded with initial escalation day and build-up phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of this data was performed. Results Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a build-up phase dose was 46%, with a risk of 29% for upper respiratory symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory (1.2%) and skin (1.1%) were the most likely symptoms after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after one home dose each. Conclusions Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare.