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

Abstract

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.

Past, present, and future of allergen immunotherapy vaccines

“…This could be achieved by the administration of hematopoietic stem cells, eventually cord blood cells, which are transfected with allergens or allergen‐derived peptides 174 . Alternatively, oral tolerance induction by feeding allergens or allergen‐derived T‐cell epitope‐containing peptides may be possible 191,192 . The latter approaches clearly involve ethical considerations and will require extensive research in experimental models, whereas the active vaccination approach of using hypoallergens could enter relatively soon clinical trials.…”

Preventive Allergen-Specific Vaccination Against Allergy: Mission Possible?

“…House dust mite allergy is by far the most important allergy affecting more than 20% of the population in Asia, Australia and many other parts of the world ( 84 , 85 ). For house dust mites a cocktail of only 6 important allergen molecules has been defined, comprising Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, and Der p 23 ( 86 , 87 ). In Middle and Southern Europe and America grass pollen allergy dominates ( 88 ) and can be approached with BM32.…”

Clinical significance of dust mite allergens

“…2T cell epitopes containing only. Such vaccines are usually considered for allergy prevention [71]. (3) Hypoallergenic vaccines, researchers mutate or even remove the IgE reaction epitopes in allergen proteins to make them non-IgE reactive, but retain the T cell epitopes and the ability to induce the production of blocking antibodies, such as the mutation of Der p 2 sequence, resulting in a significant decrease in IgE reactivity [72].…”