Treating allergies via skin – Recent advances in cutaneous allergen immunotherapy

Nesovic, Lazar D; Shakya, Akhilesh Kumar; Gill, Harvinder Singh

doi:10.1016/j.addr.2022.114458

Cited by 6 publications

(2 citation statements)

References 218 publications

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“…Recently, mechanically compromised skin has been utilized as an alternative method to induce food sensitization and provoke anaphylactic reaction in rat and mice ( 15 , 16 ). In humans, excessive tape-stripping has also been implicated in allergy exacerbation rather than achieving a therapeutic effect ( 17 ). Hence, we employed the tape-stripping process to mechanically disrupt the skin barrier and tested its ability to induce peanut sensitization in Yucatan mini pigs.…”

Section: Discussionmentioning

confidence: 99%

Development of a mini pig model of peanut allergy

Shakya,

Backus,

Nesovic

et al. 2024

Front. Allergy

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IntroductionThe prevalence of peanut allergies is increasing, emphasizing the need for an animal model to enhance our understanding of peanut allergy pathogenesis and to advance diagnostic tools and therapeutic interventions. While mice are frequently used as model organisms, their allergic responses do not fully mirror those observed in humans, warranting the exploration of a higher animal model. The porcine gastrointestinal system closely resembles that of humans, and exhibits allergy symptoms akin to human responses, making pigs a promising model for peanut allergy research.MethodsIn this study we compared two allergen sensitization protocols involving either topical allergen application after repeated tape stripping (TS) or intraperitoneal (IP) injections to induce peanut-specific allergy and anaphylaxis reactions in mini pigs. Mini pigs sensitized with a combination of peanut protein extract (PE) and cholera toxin (CT) through either the IP or the TS route.ResultsSensitized pigs via both methods developed systemic PE-specific IgG and IgE responses. Following peanut challenge via the IP route, both TS- and IP-sensitized pigs displayed allergy symptoms, including lethargy, skin rashes, vomiting, and a drop in body temperature. However, respiratory distress was observed exclusively in pigs sensitized through the TS route and not in those sensitized through the IP route. However, it is noteworthy that both groups of sensitized pigs maintained peanut hypersensitivity for up to two months post-sensitization, albeit with a reduction in the severity of allergy symptoms. Importantly, both groups exhibited sustained levels of PE-specific IgG, IgE, and elevated concentrations of mast cell protease in their blood following the IP challenges.DiscussionOverall, this study reports TS and IP as two different modes of sensitization leading to onset of peanut specific allergic reactions in mini pigs, but only the TS-sensitization led to systemic anaphylaxis (simultaneous presence of symptoms: breathing difficulty, intense skin rash, and impaired mobility). A distinctive feature of these sensitization protocols is the 100% success rate (N = 4 pigs per group) in sensitizing the subjects.

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Section: Discussionmentioning

confidence: 99%

Development of a mini pig model of peanut allergy

Shakya,

Backus,

Nesovic

et al. 2024

Front. Allergy

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“…Therefore, the studies of EPIT eld aim to increase e cacy by maximizing the passage of therapeutic agents through the skin and minimizing the allergen dose. Researchers propose a variety of innovative techniques to achieve this goal, which include nanoparticles (NPs) as drug delivery systems, microneedles coated with allergens, and fractional infrared laser ablation to create micropores in the skin (14)(15)(16). Gold nanoparticles (GNPs), offer a number of advantages as transdermal, biocompatible, and nontoxic delivery systems compared with conventional delivery methods, including improved immunogenicity, enhanced and accelerated uptake of the agents by macrophages and dendritic cells (DC), and may also serve as adjuvants and also exert an anti-in ammatory effect (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

An epicutaneous therapeutic pollen-allergen extract delivery system in the allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds

Pordel,

Haghnavaz,

Rezaee

et al. 2023

Preprint

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Background: We investigated whether gold nanoparticles (GNPs) and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) could be effective for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and nonallergenic components. Methods: BALB/c mice were sensitized to total protein extract of Platanus orientalis pollen and then epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, the total extract loaded GNPs, and the total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). We then examined the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and the mixture of its recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue. Results: The current study showed that the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, histopathological analysis of lung tissue showed that it also led to a remarkable decrease in allergic rhinitis (AR)-associated inflammation and histopathological damage. The DC-targeted group showed greatest improvement in AR-related immune factors and had no histopathological damage compared with the same dose without aptamer. Conclusion: Consequently, it seems that loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in pollen-induced AR.

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