BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein.

We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma.

A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC.

Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year.

Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.

The prevalence of sensitisation to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that, 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitised to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other, and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitised patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.

The overlapping grass and olive pollen seasons in Spain and the phenomenon of cross-reactivity can make it difficult to determine the true causative agent of seasonal allergic rhinitis when only skin prick tests with whole extracts are used. The aim of the GRAMOLE study was to determine sensitization patterns to the major grass and olive pollen allergens detected using specific recombinant IgE and to explore how this knowledge affected physicians’ choice of allergen-specific immunotherapy.

Epidemiological, observational, multicenter, cross-sectional study. Results from children under 18 years of age diagnosed with seasonal allergic rhinitis by positive skin prick tests to olive and grass pollen were analyzed. Specific IgE to Phl p 1+5, Ole e 1 and Phl p 7+12 was determined. Investigators specified the optimal composition of allergen immunotherapy before and after knowing the results of the molecular diagnosis.

A total of 281 patients with a mean age of 13.4 years were included. Double sensitization to both major allergens was found in vitro in 76% of children for an IgE cut-off point of 0.35 kU/L. When the molecular diagnosis results were known, specialists changed the composition of the prescribed immunotherapy in 52.87% of cases.

Double sensitization to grass and olive pollen is common in Spain, and also occurs in the pediatric population. Molecular diagnosis using specific IgE may help improve immunotherapy selection in polysensitized patients.

Food allergy is increasingly common in children, affecting about 4-8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization in order to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen-contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non-vascularized epidermis limits systemic absorption, contributing to the high safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper-responsiveness and immunologic parameters. Several clinical trials of EPIT have recently been completed or are on-going. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following one year of therapy is less than that seen compared to high dose (2 g – 4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears.

Sublingual immunotherapy (SLIT) has emerged as an effective and exceptionally safe method of treatment of the atopic patient. However, the optimal number of allergens that should be included in the SLIT treatment regimen for the polysensitized patient is not known and practices vary widely. This study aims to compare the efficacy of single-allergen SLIT with pauci-allergen vs multiallergen aqueous SLIT in polysensitized patients.

Sixteen subjects sensitized to 6+ allergens were enrolled in the study. Subjects were blinded and randomized to SLIT treatment groups that included 1 (single), 3 (pauci), or all sensitized allergens (multi). Allergens selected were those to which the patient was most sensitized and correlated with history. Primary outcomes included daily allergy medication use, weekly Rhinoconjunctivitis Symptom Score (RCSS), and the mini-Rhinoconjuncitivitis Quality of Life Questionnaire (m-RQLQ). All metrics were measured at baseline, 6 weeks, 3 months, 6 months, and 9 months.

There were significant decreases from baseline in RCSS and m-RQLQ scores in all study groups at each interval after beginning SLIT (p < 0.05). There was no significant decrease in number of daily allergy medications used regardless of number of allergens in patient’s treatment vial (p = 0.50). No significant differences emerged based on number of allergens used.

Single-antigen, pauci-antigen, and multiantigen aqueous SLIT significantly improved allergy symptoms. There was no significant difference observed in efficacy of single-allergen SLIT vs pauci-allergen or multi-allergen SLIT in polysensitized patients.

Occurring in both developed and developing countries and across all ethnic groups and ages allergic diseases represent a global health problem. During the last few decades, there has been an increase in the prevalence of allergic diseases and it has been predicted that by 2025 half of the entire EU population will be affected. The three major management strategies are avoidance, symptom control by pharmacotherapy and allergen immunotherapy (AIT). By contrast with symptom control by pharmacotherapy AIT aims to modify the immune system via tolerance induction and is potentially able to alter the course of allergic diseases. The potential preventive effect of AIT is currently being explored for pollen.

Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol.

In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4, and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8).

No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became non-reactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P<0.001) and V8 (12.2-fold, P<0.001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (-54.6%, P<0.001) and V8 (-71.6%, P<0.001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P<0.001) at V6 and 25% (P<0.001) at V8.

Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.

Local allergic rhinitis (LAR) is a relatively new disease.

To ascertain the effects of allergen-specific immunotherapy in LAR.

A randomized, double-blind, placebo-controlled trial of birch subcutaneous allergen immunotherapy (AIT) for LAR was performed in 28 patients. The therapy was performed for 24 months in 15 patients with AIT and 13 patients given placebo. The primary end point was decrease in symptom medication score (SMS). In addition, we monitored serum-specific immunoglobulin E (IgE), serum-specific immunoglobulin G4, nasal-specific IgE to Bet v 1, and safety and quality-of-life parameters.

After 24 months of treatment, there was a significant decrease in the median area under the curve for SMS of the active group vs the placebo group: 2.14 (range, 1.22-4.51) vs 6.21 (range, 5.12-7.89), at the P < .05 level. During AIT, the active group showed a significant decrease in SMS of up to 65% vs baseline. A significant increase in immunoglobulin G4 and decrease in nasal-specific IgE were observed in the active group during AIT compared with the placebo group. AIT was well-tolerated and without systemic reactions.

This study demonstrates that AIT for birch pollen in patients with LAR was clinically effective and exhibited good tolerance.

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.

Allergen-specific immunotherapy can induce long-term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β-glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.

Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)-driven mouse model of allergic asthma.

HDM-sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen-induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue.

ESR measurement shows suppression of early allergic response in HDM-SCIT- and DerP1/2-SCIT-treated mice. Both HDM-SCIT and DerP1/2-SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2-SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2-SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL-33, CCL17 and eotaxin levels in lung tissue.

Taken together, these data show that purified DerP1/2-SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM-induced activation of lung structural cells including airway epithelium. postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.