Wormwood (Artemisia) pollen is among the top 10 aeroallergens globally that cause allergic rhinitis and bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treating patients with allergic rhinitis, conjunctivitis, and asthma. A significant disadvantage of today’s ASIT methods is the long duration of therapy and multiplicity of allergen administrations. The goal of this study was to undertake a pilot study in mice of a novel ultrashort vaccine immunotherapy regimen incorporating various adjuvants to assess its ability to treat allergic bronchial asthma caused by wormwood pollen.We evaluated in a mouse model of wormwood pollen allergy candidates comprising recombinant Art v 1 wormwood pollen protein formulated with either newer (Advax, Advax-CpG, ISA-51) or more traditional [aluminum hydroxide, squalene water emulsion (SWE)] adjuvants administered by the intramuscular or subcutaneous route vs. intranasal administration of a mucosal vaccine formulation using chitosan-mannose nanoparticle entrapped with Art v 1 protein. The vaccine formulations were administered to previously wormwood pollen-sensitized animals, four times at weekly intervals. Desensitization was determined by measuring decreases in immunoglobulin E (IgE), cellular immunity, ear swelling test, and pathological changes in the lungs of animals after aeroallergen challenge. Art v 1 protein formulation with Advax, Advax-CpG, SWE, or ISA-51 adjuvants induced a significant decrease in both total and Art v 1-specific IgE with a concurrent increase in Art v 1-specific IgG compared to the positive control group. There was a shift in T-cell cytokine secretion toward a Th1 (Advax-CpG, ISA-51, and Advax) or a balanced Th1/Th2 (SWE) pattern. Protection against lung inflammatory reaction after challenge was seen with ISA-51, Advax, and SWE Art v 1 formulations. Overall, the ISA-51-adjuvanted vaccine group induced the largest reduction of allergic ear swelling and protection against type 2 and non-type 2 lung inflammation in challenged animals. This pilot study shows the potential to develop an ultrashort ASIT regimen for wormwood pollen-induced bronchial asthma using appropriately adjuvanted recombinant Art v 1 protein. The data support further preclinical studies with the ultimate goal of advancing this therapy to human clinical trials.

Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis, conjunctivitis, and asthma. A disadvantage of current ASIT methods is the length of therapy which requires numerous allergen administrations. The success of ASIT is determined by its schedule, which, depending on the vaccine and type of allergy, can be pre-seasonal (before the allergy season begins), combined pre/co-seasonal (during the allergy season) etc. The aim of the present study was to evaluate a vaccine based on recombinant Artemisia vulgaris pollen major Art v 1 protein formulated with ISA-51 adjuvant for therapy of allergic rhinitis and bronchial asthma in Artemisia-sensitized mice in an ultrashort (4 subcutaneous injections at weekly intervals) pre- and co-seasonal ASIT regimen.To simulate co-seasonal ASIT in mice, mice were regularly challenged with intranasal and nebulized Artemisia vulgaris pollen extract at the same time as receiving subcutaneous ASIT. For comparison, we used a previous Art v 1 protein vaccine formulated with SWE adjuvant, which in this study was modified by adding CpG oligonucleotide (Th1-biasing synthetic toll-like receptor 9 agonist), and a commercial vaccine containing a modified Artemisia vulgaris extract with aluminum hydroxide adjuvant. The therapeutic potential of Art v 1 based vaccine formulations with different ASIT regimens was evaluated in high and low (10 times lower) dose regimens.The ISA-51-adjuvanted vaccine formulations were the only ones among those studied in the ultrashort pre- and co-seasonal ASIT regimens to provide significant reduction in both signs of allergic rhinitis and bronchial asthma in sensitized mice (vs. positive control). In the ISA-51 adjuvanted group, immune response polarization toward Th1/Treg was observed in pre-seasonal ASIT, as reflected in a significant decrease in the serum level of total and Art v 1-specific IgE and increased ratios of allergen-specific IgG2a/IgG1 and IFN-γ/IL-4. The high dose SWE-CpG-adjuvanted vaccine had similar efficacy to the ISA-51 adjuvanted groups whereas the commercial vaccine showed significantly less effectiveness.The findings support further preclinical safety studies of the Art v 1-based vaccine formulated with ISA-51 adjuvant.

It remains unclear whether gym customers are exposed to any nickel from the metal equipment and if the exposure is associated with the duration of contact. Therefore, the aim of this study was to ascertain exposure to nickel measured through nickel concentration in the hair in those exercising in a fitness gym. We enrolled 100 amateur athletes in one of the gyms in Almaty, Kazakhstan (all men, median age 30 (interquartile range (IQR) 10) years), exercising from 2 to 7 days a week for 40 to 180 minutes and their age- and sex-matched controls who did not exercise. All subjects filled in the questionnaires on the exercising patterns, smoking and occupational exposure and then donated 0.25 g of head hair, in which nickel was measured using atomic absorption spectrophotometry. Hair nickel concentration ranged from 0 to 8.5 µg/g with notable left-skewness towards low concentrations in both groups. Hair nickel concentration was not associated with age, smoking or occupation, but was significantly lower in amateur athletes compared to controls (median 0 (IQR 0.5) vs. 0.9 (IQR 1.4) µg/g). More days a week in a gym, longer workout history, longer workout duration or supplements use did not increase the probability of being stratified in a high-exposure subgroup (defined as 75th percentile of hair nickel concentration and higher); however, there were more smokers in a low-exposure group (p<0.05). With the mixed pattern of exposure, gym goers may be unlikely exposed to more nickel from the metal equipment in the gym, however the exposure may depend on the specific alloy composition.