Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Campana, Raffaela; Moritz, Katharina; Neubauer, A.; Huber, Hanspeter; Henning, Rainer; Brodie, Tess M.; Kaider, Alexandra; Sallusto, Federica; Wöhrl, Stefan; Valenta, Rudolf

doi:10.1038/s41598-017-10278-1

Cited by 19 publications

(19 citation statements)

References 30 publications

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“…Among the conventional AIT delivery options (subcutaneous or sublingual), we compared TDIT only with SCIT in this study. A recent study of epicutaneous immunotherapy (EPIT) reported advantages compared with SLIT 22 . To demonstrate the merits of TDIT, a comparative study with SLIT is necessary.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of transdermal immunotherapy with biodegradable microneedle patches in a murine asthma model

Park

Han

et al. 2020

Clin Experimental Allergy

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Background House dust mite (HDM) is a well‐known cause of asthma. Allergen‐specific immunotherapy (AIT) can only modify the natural course of the disease. Conventional routes of HDM AIT are subcutaneous or sublingual. Subcutaneous immunotherapy (SCIT) has a disadvantage of systemic hypersensitive reaction, and the sublingual immunotherapy has a disadvantage of local allergic reaction and low drug adherence. Objective To overcome the weak points of conventional AIT, we developed a HDM loaded biodegradable microneedle patch (MNP) for transdermal immunotherapy (TDIT). We aim to demonstrate the efficacy of TDIT in murine asthma model triggered by HDM compared with conventional SCIT. Methods To make HDM asthma mouse model, 5‐week‐old BALB/c female mice were sensitized and challenged by intranasal administration of HDM. The mice were divided into 5 groups: sham, asthma, low (10 µg) and high dose (100 µg) SCIT, and TDIT (10 µg). To make HDM loaded MNP, droplet‐born air blowing method was used. Airway hyperresponsiveness and allergic inflammation markers were analysed by bronchoalveolar lavage fluid, immunohistochemistry, serum immunoglobulin (Ig) analysis, and lung cytokine assays. Results Airway hyperresponsiveness was ameliorated by TDIT. Eosinophilic inflammation in bronchoalveolar lavage was improved without adverse reactions. Reduction of Th2 (IL‐4, IL‐5, and IL‐13) cytokines, and HDM‐specific IgE, induction of Treg (IL‐10, TGF‐β), Th1 (IFN‐γ) cytokines were observed. Eosinophilic infiltration, goblet cell hyperplasia, and subepithelial fibrosis were also alleviated by TDIT. These changes were more significant in the TDIT group than in subcutaneous AIT group. Conclusion In conclusion, HDM loaded biodegradable TDIT is a novel treatment option to treat asthma which showed more effectiveness and may have better safety profiles than conventional SCIT.

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Section: Discussionmentioning

confidence: 99%

Efficacy of transdermal immunotherapy with biodegradable microneedle patches in a murine asthma model

Park

Han

et al. 2020

Clin Experimental Allergy

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“…The levels of G‐CSF, GM‐CSF, IFN‐gamma, IL‐1 beta, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12 (p70), IL‐13, IL‐17, MCP‐1, MIP‐1beta, and TNF‐alpha were measured in supernatants of 7 day PBMC cultures by Luminex multiplex assay (Bio‐Plex Pro™ Human Cytokine 17‐plex Assay; Bio‐Rad) according to the manufacturer's instructions as described . The Bio‐Plex ® 200 System (Bio‐Rad) was used for analysis.…”

Section: Methodsmentioning

confidence: 99%

A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens

Huang

Curin

Banerjee

et al. 2019

Allergy

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Background: Inthehousedustmite(HDM)Dermatophagoides pteronyssinus,Derp 1,2,5,7,21,and23havebeenidentifiedasthemostimportantallergens.Theaimof thisstudywastodefinehypoallergenicpeptidesderivedfromthesequencesofthe sixallergensandtousethepeptidesandthecompleteallergenstostudyantibody, Tcell,andcytokineresponsesinsensitizedandnonsensitizedsubjects. Methods: IgE reactivity of HDM-allergic and non-HDM-sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirtythree peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP,respectively.Allergenicactivitywasdeterminedbybasophilactivation. CD4+TcellandcytokineresponsesweredeterminedinPBMCculturesbyCFSEdilu-tionandLuminextechnology,respectively. Results: HousedustmiteallergicsshowedIgEreactivityonlytocompleteallergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity.IgGantibodiesofHDM-allergicandnonsensitizedsubjectsweredirectedagainst peptideepitopesandhigherallergen-specificIgGlevelswerefoundinHDMallergics. PBMCfromHDM-allergicsproducedhigherlevelsofIL-5whereasnon-HDM-sensitized individuals mounted higher levels of IFN-gamma, IL-17, pro-inflammatory cytokines,andIL-10. Conclusion: IgG antibodies in HDM-allergic patients recognize peptide epitopes whicharedifferentfromtheepitopesrecognizedbyIgE.Thismayexplainwhynaturallyoccurringallergen-specificIgGantibodiesdonotprotectagainstIgE-mediated allergicinflammation.AmixofhypoallergenicpeptidescontainingTcellepitopesof themostimportantHDMallergenswasidentified. K E Y W O R D Sallergen,housedustmiteallergy,recombinantallergen,syntheticpeptide,Tcellepitope ThisisanopenaccessarticleunderthetermsoftheCreativeCommonsAttribution-NonCommercialLicense,whichpermitsuse,distributionandreproduction inanymedium,providedtheoriginalworkisproperlycitedandisnotusedforcommercialpurposes.

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“…Bound IgE was detected as described [ 25 ]. IgG 4 antibody levels specific for rApi m 1 and rVes v 5 were measured in 1:40 diluted serum samples by ELISA as described [ 26 ]. IgE(kU A /L)/IgG 4 (OD) ratios for Ves v 5 were calculated as described [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

The culprit insect but not severity of allergic reactions to bee and wasp venom can be determined by molecular diagnosis

et al. 2018

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BackgroundAllergy to bee and wasp venom can lead to life-threatening systemic reactions. The identification of the culprit species is important for allergen-specific immunotherapy.ObjectivesTo determine a panel of recombinant bee and wasp allergens which is suitable for the identification of bee or wasp as culprit allergen sources and to search for molecular surrogates of clinical severity of sting reactions.MethodsSera from eighty-seven patients with a detailed documentation of their severity of sting reaction (Mueller grade) and who had been subjected to titrated skin testing with bee and wasp venom were analyzed for bee and wasp-specific IgE levels by ImmunoCAPTM. IgE-reactivity testing was performed using a comprehensive panel of recombinant bee and wasp venom allergens (rApi m 1, 2, 3, 4, 5 and 10; rVes v 1 and 5) by ISAC chip technology, ImmunoCAP and ELISA. IgG4 antibodies to rApi m 1 and rVes v 5 were determined by ELISA and IgE/IgG4 ratios were calculated. Results from skin testing, IgE serology and IgE/IgG4 ratios were compared with severity of sting reactions.ResultsThe panel of rApi m 1, rApi m 10, rVes v 1 and rVes v 5 allowed identification of the culprit venom in all but two of the 87 patients with good agreement to skin testing. Severities of sting reactions were not associated with results obtained by skin testing, venom-specific IgE levels or molecular diagnosis. Severe sting reactions were observed in patients showing < 1 ISU and < 2kUA/L of IgE to Api m 1 and/or Ves v 5.ConclusionWe identified a minimal panel of recombinant bee and wasp allergens for molecular diagnosis which may permit identification of bee and/or wasp as culprit insect in venom-sensitized subjects. The severity of sting reactions was not associated with parameters obtained by molecular diagnosis.

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Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Cited by 19 publications

References 30 publications

Efficacy of transdermal immunotherapy with biodegradable microneedle patches in a murine asthma model

Efficacy of transdermal immunotherapy with biodegradable microneedle patches in a murine asthma model

A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens

The culprit insect but not severity of allergic reactions to bee and wasp venom can be determined by molecular diagnosis

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