Oral Peanut Challenge Research Articles

A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice

The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized Collaborative Cross strain CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, in contrast to C3H/HeJ (C3H) mice. This study aimed to determine the genetic basis of orally induced anaphylaxis to peanut in CC027 mice. A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. Atotal of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 mice and 5 additional Collaborative Cross strains. Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis and 4% having severe anaphylaxis. There were 8 genetic loci associated with variation in response to peanut challenge-6 associated with anaphylaxis (temperature decrease) and 2 associated with peanut-specific IgE levels. There were 2 major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis gene. Consistent with described functions of Themis, we found that CC027 mice have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. Our results demonstrate a key role for Themis in the orally reactive CC027 mouse model of peanut allergy.

High Degree of Desensitization After 1 Year of Early-Life Peanut Oral Immunotherapy: Small Children Oral Immunotherapy (SmaChO) Randomized Controlled Trial

BackgroundThe prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut – daily oral intake of an initially low and then increasing dose of peanut - often show problematic side effects but there are indications of better safety and effect in younger children compared with older children and adults. ObjectiveTo determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose, in peanut allergic children 1-3 years of age, a 1-year interim analysis. MethodsIn a randomized controlled trial (2:1 ratio) 75 children with median age 31 months (IQR 23 – 40) were assigned to receive peanut oral immunotherapy (OIT) (n=50) or peanut avoidance (n=25). ResultsIn the OIT group and the avoidance group, 43/50 and 20/25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after one year was tolerated by 72% (36/50) in the OIT-group compared to 4% (1/25) in the avoidance-group, p<0.001. Median tolerated cumulative dose was 2750 mg (IQR 275 – 5000) peanut protein in the OIT-group compared to 2.8 mg (IQR 0.3 – 27.8) in the avoidance-group, p<0.001. Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events, 79% were mild, and three doses of epinephrine were given at home to two individuals. ConclusionIn children 1-3 years of age, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after one year. ClinicalTrials.govNCT04511494

Exploring parental interest in a single, low-dose oral peanut challenge for their children with peanut allergy

Exploring parental interest in a single, low-dose oral peanut challenge for their children with peanut allergy

A phase 2 study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis.

IgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways, and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA-approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy. After undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received four standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut protein to elicit an objective clinical reaction. At baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range, 444 - 4,044 mg). Seven patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. Three patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious. Acalabrutinib pretreatment achieved clinically-relevant increases in patients' tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials. gov NCT05038904FUNDING. AstraZeneca Pharmaceuticals, the Johns Hopkins Institute for Clinical and Translational Research, the Ludwig Family Foundation, and NIH grants AI143965 and AI106043.

Reactions to peanut at first introduction in infancy are associated with age ≥8 months and severity of eczema.

Previous studies have shown the efficacy of the early introduction of peanut to prevent peanut allergy. Due to the exclusion of infants with sensitization to peanut, it remains unclear what the optimal timing of introduction is. The PeanutNL study was performed in 6 pediatric allergology centers in the Netherlands. Infants referred for the clinical early introduction of peanut to prevent peanut allergy underwent skin prick tests for peanut and an oral peanut challenge at a median age of 6 months. One hundred sixty two of 707 infants (23%) who had never eaten peanut before were sensitized to peanut, of which 80 (49%) had wheals of >4 mm. Sixty seven of 707 infants (9.5%) had a positive oral challenge to peanut at first introduction. Multivariate analysis revealed that age (p < .001) and SCORAD eczema severity scores (p = .001) were significant risk factors. Introduction of peanut at ≥8 months in infants with moderate and severe eczema resulted in an increased risk (odds ratio 5.24 (p = .013) and 3.61 (p = .019), respectively) of having reactions to peanut as compared to introduction before 8 months. A family history of peanut allergy and previous reactions to egg were not identified as independent risk factors. These results suggest that peanut should be introduced before the age of 8 months to reduce the risk of reactions at first exposure in infants with moderate and severe eczema. Furthermore, since children with severe eczema have the highest risk of reactions, the clinical introduction of peanut should be considered, at the latest at the age of 7 months.

The Likelihood of Sustained Unresponsiveness Following Peanut Oral Immunotherapy is Linked to The Frequency of Granzyme B+ Memory CD8+ T Cells

Participants successfully desensitized to peanut through the 2-year-long peanut OIT trial POISED were classified as sustained unresponsive (SU) vs. desensitized alone (DS) based upon oral peanut challenge outcome following a 3-month peanut avoidance period post-OIT. Mass cytometry-based phenotyping of PBMCs from these participants showed that a lower frequency of naïve CD8+ T cells positively associates with sustained unresponsiveness. We further probed CD8+ T cells from SU and DS participants to understand molecules and pathways influencing peanut tolerance.

Effects of Exercise and Sleep Deprivation on Reaction Severity During Oral Peanut Challenge: A Randomized Controlled Trial

The severity of allergic reactions to foods can vary markedly. Little is known of variations in reaction severity within or between individuals or the effects of cofactors. We examined the effects of sleep deprivation and exercise and repeat challenges on the severity and patterns of allergic reactions to peanut. In a randomized crossover study, adults with peanut allergy underwent 3 open peanut challenges in random order: with exercise after each dose, with sleep deprivation preceding challenge, and with no intervention. The primary outcome was eliciting dose, reported elsewhere. Reaction severity was a secondary outcome, evaluated using a weighted log-transformed numerical severity score. Analyses estimated the difference in severity between nonintervention challenge and challenges with exercise or sleep deprivation, adjusting for challenge order and using the highest dose tolerated by each individual across all their challenges. Symptom pattern reproducibility was assessed by comparing symptom sequences using pairwise sequence alignment to obtain a percentage match in symptom pattern. Eighty-one participants (mean age 25 y) completed at least 1 postbaseline challenge. Sleep deprivation, but not exercise, significantly increased severity score by 48% (95% CI 12%-84%; P= .009) compared with no intervention. A 38% increase in severity was observed between the first and the lastpostbaseline challenge (95% CI 1%-75%; P= .044). Theaverage pairwise match of symptoms within individuals was 82.4% and across individuals was 78.3%. A novel severity score demonstrates that sleep deprivation and repeated challenges increase reaction severity. Understanding factors affecting severity is essential for effective risk management. We also show that symptom patterns in repeat peanut challenges are similar within and between individuals.

Implementation of the Addendum Guidelines for Peanut Allergy Prevention by US Allergists, A Survey Conducted by the NIAID, in Collaboration With the AAAAI

To assess peanut feeding guideline implementation by US allergists who manage infants with food allergies.US allergists within the American Academy of Allergy, Asthma, and Immunology database.This was a cross-sectional survey conducted electronically between September and October 2018. The survey consisted of 31 questions, of which 4 were used to screen out those who were not practicing, did not see infants ≤12 months old, did not manage food allergy, and were not board certified. The survey was performed ∼21 months after the guidelines were published and ∼3 and one-half years after publication of the Learning Early About Peanut Allergy (LEAP) study.Over 3200 surveys were delivered by e-mail. There was a return rate of 29% (n = 825), of which 789 were completed enough for analysis. Nearly all respondents (99%) advised parents on peanut allergy prevention and performed in vitro or in vivo testing for peanut-specific immunoglobulin E. Nearly all strongly agreed (69%) or agreed (28%) that early introduction was effective in preventing peanut allergy. A total of 97% were aware of the guidelines. Of those, 65% reported rare deviation from the guidelines, and 34% reported partial implementation. The deviations reported erred on the side of caution, not nonchalance. Three clinical scenarios of severe eczema and a positive skin-prick test (SPT) result to peanut were described and included in the survey. Respondents fully adhered to the guidelines when the diameter of the peanut SPT was small (0–2 mm; 75.4%) or large (≥8 mm; 78%). Somewhat fewer (68.6%) fully adhered when the peanut SPT was 3 to 7 mm diameter. Only 44% fully adhered to the guidelines in all 3 scenarios. As compared with older allergists (≥31 years since med school graduation), younger allergists (0–10 years since graduation) were more likely to use the guidelines as published (P = .012), perform graded oral peanut challenges (P < .0001), perform single dose in-office challenges (P = .0012), strongly agree that early peanut introduction conferred protection against the development of allergy (P = .0003), and have read the full guideline (P = .0008). Older respondents were more likely to desire more training on the guidelines (P = .001) and report that conducting graded challenges (P = .0008) and reimbursement (P < .0001) were barriers to implementation. Allergists in academic institutions were more aligned with the younger allergists but identified a lack of clinic time as a barrier to implementation (P < .0001). In contrast, nonacademically affiliated allergists were more likely to identify concern about allergic reactions (P < .0001) and legal liability (P < .0001) as barriers.Most allergists are aware of and implement guidelines regarding early introduction of peanut, but barriers to full implementation remain.One can look at these results as good news that so many allergists generally adhered to the guidelines ∼21 months after publication or as bad news that so many more did not. Because the LEAP study was published 2 years before the guidelines, many allergists had already started to adjust practices by the time the guidelines were published. I will say the glass is half full because implementation of these guidelines was much faster than implementation of guidelines for asthma care when the first expert panel report was published 30 years ago. One weakness of this study published in 2020 is that the survey was conducted 2 years before publication. The results might differ by now, but how? Guidelines are just that: advice based on scientific principles. They are not rules or laws, so they must be open to interpretation and adjustment as knowledge evolves and experience grows. Finally, as someone who graduated from medical school 38 years ago, I found it interesting that older allergists were less likely to follow the guidelines than those who were more recently trained. Might it be because their greater experience made them interpret the nuances of the guidelines differently? Or might it be that greater efforts should be made to target older and nonacademically affiliated allergists when new guidelines are published? If either of those or any other explanation is correct, I would not extrapolate from peanut allergy and allergists to other guidelines or specialties.

Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations

The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain's susceptibility is not known. We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.

Biomarkers of severity and threshold of allergic reactions during oral peanut challenges

BackgroundOral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity.ObjectiveOur aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut.MethodsWe assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC.ResultsWhen a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients.ConclusionsThe BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.

CONTINUOUS LIKELIHOOD RATIOS TO PREDICT THE PROBABILITY OF A PEANUT REACTION

Introduction Peanut-specific IgE (PsIgE) is used to predict the probability of a reaction using likelihood ratios (LR) which convert pretest to posttest probabilities. While dichotomous (positive or negative) LRs are defined using a cutoff of 0.35, it is better to use a continuous LR which corresponds to each value of PsIgE. This is particularly important when there is only a PsIgE and no history of prior ingestion to rely on. Methods PsIgEs were measured and oral peanut challenges performed on 58 children ages 9 months to 18 years. An ROC curve was determined using SPSS. The slope of the ROC curve, which is the likelihood ratio for each value of PsIgE, was determined by differentiated the ROC curve and used to convert sIgEs to likelood ratios. Results PsIgE ranged from 0 to 23. There were 33 negative and 25 positive oral challenges. The area under the ROC curve was 0.71 (p Conclusions Continuous LRs can provide a more accurate assessment of the probability of a peanut reaction for a given sIgE when the history of peanut ingestion is not known. Additional data points will refine these estimates.

Feasibility of desensitizing children highly allergic to peanut by high-dose oral immunotherapy.

There are limited data on the feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts. In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000mg peanut protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs) and determine factors associated with reaching a maintenance dose. The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15years old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until reaching MMD or IMD and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol deviations were explored for associations with reaching maintenance dose. All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG4 /s-IgE ratio (OR [95% CI]: 1.02 [1.00, 1.04]) was associated with reaching MMD. Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25-5g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited the feasibility of reaching MMD.

Severity and threshold of peanut reactivity during hospital-based open oral food challenges: An international multicenter survey.

Peanut allergy is classically managed by food avoidance. Immunotherapy programs are available at some academic centers for selected patients reacting to small amounts of peanut during food challenge. We aimed to determine and compare reaction thresholds and prevalence of anaphylaxis during peanut oral challenges at multiple specialist allergy centers. A retrospective, international survey of anonymized case records from seven specialist pediatric allergy centers from the UK and Ireland, as well as the Australian HealthNuts study. Demographic information, allergy test results, reaction severity and threshold during open oral peanut challenges were collated and analyzed. Of the 1634 children aged 1-18years old included, 525 (32%) failed their peanut challenge. Twenty-eight percent reacted to 25mg, while 38% only reacted after consuming 1g or more of whole peanut. Anaphylaxis (55 [11%]) was 3 times more common in teenagers than younger children and the likelihood increased at all ages as children consuming more peanut at the challenge. Children who developed anaphylaxis to 25-200mg of whole peanut were significantly older. Previous history of reaction did not predict reaction threshold or severity. More than a third of the children in this large international cohort tolerated the equivalent of one peanut in an oral challenge. Anaphylaxis, particularly to small amounts of peanut, was more common in older children. Tailored immunotherapy programs might be considered not only for children with low, but also higher reaction thresholds. Whether these programs could prevent heightened sensitivity and anaphylaxis to peanut with age also deserves further study.

Conjunctival provocation test in diagnosis of peanut allergy in children.

Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

Oral Peanut Challenges in Infants

Oral Peanut Challenges in Infants

Antigen Absorption is Correlated With Allergic Reaction Severity Upon Oral Peanut Challenge in Mice

Antigen Absorption is Correlated With Allergic Reaction Severity Upon Oral Peanut Challenge in Mice

Relative Value of Skin Prick, Specific Peanut Specific IgE and Component Tests in Predicting the Outcome of Oral Peanut Challenge

Relative Value of Skin Prick, Specific Peanut Specific IgE and Component Tests in Predicting the Outcome of Oral Peanut Challenge

Utility of Specific IgE to Ara h 2 in Italian Allergic and Tolerant Children Sensitized to Peanut.

Emerging data suggest that measurement of serum IgE to peanut components can be clinically helpful and more accurate than IgE to whole peanut to predict peanut allergy. Not all studies have used prospective samples, multiple components and oral challenges. Currently, there are no data on this topic involving Italian children. 32 patients (23 males; median age 9 years) with reported history for peanut allergy and evidence of peanut sensitization (skin prick test to peanut extract ≥ 3mm) have been analyzed for serum IgE to whole peanut and recombinant allergen components Ara h 1, 2, 3, 8, and 9 with Immuno CAP and completed an open oral food challenge with peanut. 12 (37.5%) children had a positive challenge to peanut and were considered allergic. No differences were seen between the median values of IgE to peanut, Ara h 1, 3, 8 and 9 in allergic and tolerant children to peanut challenge. Noteworthy, 5 of 20 tolerant children had IgE to peanut> 15 kUA/l which is commonly considered a predictive value of peanut allergy. Conversely, a significant difference was seen when comparing the median value of IgE to Ara h 2 in the two groups: 0.75 kUA/l (IQR: 0.22-4.34 kUA/l) in allergic children versus 0.1 kUA/l (IQR: 0.1-0.12 kUA/l) in tolerant ones (P< 0.001). IgE levels to Ara h 2 are significantly higher in children that react to oral peanut challenge. Our findings in Italian children have been in line with recent reports in various populations of Northern Europe, the US and Australia and add confirmatory evidence that analysis of IgE to Ara h 2 could reduce the need for peanut challenge in suspected allergic patients.

Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy

Treatments to reverse peanut allergy remain elusive. Current clinical approaches using peanut oral/sublingual immunotherapy are promising, but concerns about safety and long-term benefit remain a barrier to wide use. Improved methods of delivering peanut-specific immunotherapy are needed. We sought to investigate the efficacy and safety of peanut oral immunotherapy using CpG-coated poly(lactic-co-glycolic acid) nanoparticles containing peanut extract (CpG/PN-NPs) in a murine model of peanut allergy. C3H/HeJ mice were rendered peanut allergic by means of oral sensitization with peanut and cholera toxin. Mice were then subjected to 4 weekly gavages with CpG/PN-NPs, vehicle (PBS), nanoparticles alone, peanut alone, CpG nanoparticles, or peanut nanoparticles. Untreated mice served as naive controls. After completing therapy, mice underwent 5 monthly oral peanut challenges. Anaphylaxis was evaluated by means of visual assessment of symptom scores and measurement of body temperature and plasma histamine levels. Peanut-specific serum IgE, IgG1, and IgG2a levels were measured by using ELISA, as were cytokine recall responses in splenocyte cultures. Mice with peanut allergy treated with CpG/PN-NPs but not vehicle or other treatment components were significantly protected from anaphylaxis to all 5 oral peanut challenges, as indicated by lower symptom scores, less change in body temperature, and a lower increase of plasma histamine levels. Importantly, CpG/PN-NP treatment did not cause anaphylactic reactions. Treatment was associated with a sustained and significant decrease in peanut-specific IgE/IgG1 levels and an increase in peanut-specific IgG2a levels. Compared with vehicle control animals, peanut recall responses in splenocyte cultures from nanoparticle-treated mice showed significantly decreased levels of TH2 cytokines (IL-4, IL-5, and IL-13) but increased IFN-γ levels in cell supernatants. Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategyfor peanut-specific immunotherapy in human subjects.

Severity of Reactions to Oral Peanut Challenges in Children and Adults

Severity of Reactions to Oral Peanut Challenges in Children and Adults