Endo-lysosomal-targeted constructs comprising dust MITE allergens methods and uses thereof

Abstract

The present invention relates to endo-lysosomal-targeted nucleic acid constructs encoding HDM allergens, preferably at least three allergens, and endo-lysosomal-targeting polypeptides as well as methods and uses thereof, particularly in AIT-methods relating to HDM allergies.

Description

New PCT-patent applicationApplicants: Helmholtz Zentrum MuenchenTechnical University of MunichAllergopharma GmbH & Co. KGOur ref: HEL18334PCTDate: 17 April 2026ENDO-LYSOSOMAL-TARGETED CONSTRUCTS COMPRISING DUST MITE ALLERGENS METHODS AND USES THEREOFSEQUENCE LISTING

[0001] This application contains a Sequence Listing in computer readable form, which is incorporated herein by reference.TECHNICAL FIELD OF THE INVENTION

[0002] The present invention is in the field of allergies and relates to means and methods relating to treatment allergies, particularly to treatment of house dust mite (HDM) allergies. The present invention further relates to endo-lysosomal-targeted nucleic acid constructs encoding HDM allergens (e.g., at least three allergens) and endo-lysosomal-targeting polypeptides as well as methods and uses thereof, particularly in allergen immunotherapy (AIT)-methods relating to HDM allergies.BACKGROUND OF THE INVENTION

[0003] The available desensitization means and preparations are typically made from the feces and / or bodies of house dust mites and are insufficently effective. The cause of the low efficacy is difficult to pinpoint due to the heterogeneity of the HDM natural extract alone; a possible reason is that the crucial allergens are present in insufficient quantities or contain substances that interfere with the success of the therapy. Another problem with available desensitizations is the risk of anaphylaxis (i.e. , shock reaction to the allergen) following the administration of the therapy allergen, which is why the dose of allergens in allergen immunotherapy (AIT) preparations is recommended to be kept low, or complex and time-consuming dose increases are to be performed. Another known problem issue is that the initial administration of the allergen typically leads to an increase in allergen-specific IgE.

[0004] Therefore, there is an ongoing need to improve AIT preparations, especially by providing novel and improved constructs and compositions. The technical problem therefore is to comply with this need.

[0005] EP 2200646 A1 discloses RNA vaccines encoding allergens from selected organisms. WO 2004 / 019978 A1 and EP 3795688 A1 disclose recombinant allergens and nucleic acids, in particular DNA, encoding the same.SUMMARY OF THE INVENTION

[0006] The technical problem is solved by the subject-matter as defined in the claims. While some house dust mite allergens are known and there are major allergens to which most patients react as well as mid-tier and minor allergens to which only some patients respond, the inventive concept of the pending invention inter alia lies in demonstrating that only the three major allergens / constructs according to the pending invention are sufficient to suppress the reaction to the mite extract-induced allergy. In other words, the three mite allergens / constructs of the pending invention are sufficient to also suppress all other mite allergens contained in the extract or to induce tolerance thereto. Since there are no established models for the mechanism of tolerance induction the pending invention also relates to in vitro and in vivo models for the mechanism of tolerance induction.

[0007] In one aspect the present invention relates to a nucleic acid construct, preferably a RNA construct, comprising or consisting of the following sequences (a), (b), (d) and optionally (c), wherein said sequences are in-frame, preferably in the following order, wherein:

[0008] a) a nucleic acid sequence encoding for a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1, further preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2;

[0009] b) a nucleic acid sequence encoding for one or more house dust mite polypeptides, preferably allergens, comprising one or more of the following (or selected from the group consisting of):

[0010] i) a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of: (a’)-(c’), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01:

[0011] a’) SEQ ID NO: 5;

[0012] b’) SEQ ID NO: 4; and

[0013] c) SEQ ID NO: 3;

[0014] ii) a polypeptide comprising or consisting of one or more Derp 1-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 6-283, 682-723;

[0015] iii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite polypeptide selected from the group consisting of: (a”)-(c”), preferably said polypeptide has anantigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01:

[0016] a”) SEQ ID NO: 284;

[0017] b”) SEQ ID NO: 285; and

[0018] c”) SEQ ID NO: 286;

[0019] iv) a polypeptide comprising or consisting of one or more Der f 1 -derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 287-448;

[0020] v) a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0021] vi) a polypeptide comprising or consisting of one or more Der p 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 450-534, 724-743;

[0022] vii) a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide of SEQ ID No. 535, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0023] viii) a polypeptide comprising or consisting of one or more Der f 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 536-620;

[0024] ix) a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0025] x) a polypeptide comprising or consisting of one or more Der p 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 622-647;

[0026] xi) a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NOs: 648 or 744, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01 :01 ;

[0027] xii) a polypeptide comprising or consisting of one or more Der f 23-derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 649-672;

[0028] c) optionally, a nucleic acid sequence encoding for one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673;

[0029] d) a nucleic acid sequence encoding for:

[0030] d’) one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; and

[0031] d”) one or more cytosolic domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1;

[0032] preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.

[0033] In a further aspect the nucleic acid construct of the present invention relates to a construct encoding for an enzymatically inactive polypeptide.

[0034] In a further aspect the nucleic acid construct of the present invention relates to a construct encoding for a polypeptide comprising or consisting of a polypeptide selected from the group consisting of: SEQ ID NOs: 676-681, 682-723, 724-743.

[0035] In a further aspect the nucleic acid construct of the present invention relates to a construct wherein said nucleic acid is a RNA molecule, preferably a mRNA molecule, further preferably said RNA is a monocistronic or polycistronic mRNA molecule.

[0036] In a further aspect the nucleic acid construct of the present invention relates to a construct wherein said nucleic acid comprises one or more modified nucleosides, preferably said one or more modified nucleosides are one or more pseudouridine residues comprising (or selected fromthe group consisting of): ml^P (1 -methylpseudouridine); mlacpS^P (1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine); ^Pm (2'-0-methylpseudouridine); m5D (5-methyldihydrouridine); 5-(P-D-Ribofuranosyl)pyrimidine-2,4(1 / 7,3 / - / )-dione; mS^P (3-methylpseudouridine); and / or any combination thereof.

[0037] In a further aspect the nucleic acid construct of the present invention relates to a construct wherein said nucleic acid is an endo-lysosomal-targeted mRNA molecule.

[0038] In a further aspect the nucleic acid construct of the present invention relates to a polypeptide comprising or consisting of one or more of the following polypeptide sequences, preferably in the following order:

[0039] a) a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1, further preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2;

[0040] b) one or more house dust mite polypeptides selected from the group consisting of:

[0041] i) a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of: (a’)-(c’), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01:

[0042] a’) SEQ ID NO: 5;

[0043] b’) SEQ ID NO: 4; and

[0044] c) SEQ ID NO: 3;

[0045] ii) a polypeptide comprising or consisting of one or more Derp 1-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 6-283, 682-723;

[0046] iii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite polypeptide selected from the group consisting of: (a”)-(c”), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01:

[0047] a”) SEQ ID NO: 284;

[0048] b”) SEQ ID NO: 285; and

[0049] c”) SEQ ID NO: 286

[0050] iv) a polypeptide comprising or consisting of one or more Der f 1-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02,HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 287-448;

[0051] v) a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0052] vi) a polypeptide comprising or consisting of one or more Der p 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 450-534, 724-743;

[0053] vii) a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide of SEQ ID NO: 535, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0054] viii) a polypeptide comprising or consisting of one or more Der f 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 536-620;

[0055] ix) a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01;

[0056] x) a polypeptide comprising or consisting of one or more Der p 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 622-647;

[0057] xi) a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NOs: 648 or 744, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01 :01 ;

[0058] xii) a polypeptide comprising or consisting of one or more Der f 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 649-672;

[0059] c) optionally, one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673;

[0060] d) one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; and one or more cytosolic domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1; preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.

[0061] In a further aspect the polypeptide of the present invention relates to a polypeptide comprising or consisting of a polypeptide selected from the group consisting of: SEQ ID NOs: 676-681, 682-723, 724-743.

[0062] In a further aspect the present invention relates to an isolated cell, plurality of said isolated cells, lipid nanoparticles (LNPs) or polymersomes comprising and / or expressing one or more of the nucleic acid construct / s and / or one or more of the polypeptides of the present invention.

[0063] In a further aspect the polypeptide of the present invention is obtained or translated from / by the nucleic acid construct, cell, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of any one of the preceding claims, preferably said obtained comprises synthesising via an in vitro transcription (IVT).

[0064] In a further aspect the present invention relates to a composition comprising one or more of the nucleic acid construct / s, polypeptide / s, cell / s, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of the present invention, preferably said composition is a diagnostic, pharmaceutical composition, immune-therapeutical composition, allergen immunotherapy (AIT) composition, in vitro transcription composition (IVT composition), delivery composition and / or vaccine composition, further preferably said composition is selected from a group consisting: AIT-, IVT- and vaccine composition, most preferably said said composition is a vaccine composition.

[0065] In a further aspect the present invention relates to a method for one or more of the following: treatment, amelioration or prophylaxis of allergy; increasing tolerance to dust mites; and / or for reducing a serum allergen-specific IgE level in a subject; said method comprising administering a therapeutically effective amount of one or more of the nucleic acid construct / s, polypeptide / s, cell / s, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of any one of preceding claims to a subject in need thereof, optionally said subject has a serum allergen-specific lgE>0.35 kll / L against an allergen derived from the dust mites, preferably said subject is a mammal, further preferably said subject having an allergy, a dust mite allergy, an allergic rhinitis, allergic asthma, and / or an allergic rhinitis is caused by a house dust mite, most preferably said subject is a human.

[0066] In a further aspect the present invention relates to the nucleic acid construct, polypeptide, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of the present invention, for use as a medicament and / or in therapy.

[0067] In a further aspect the present invention relates to a nucleic acid construct, polypeptide, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of the present invention, for use in one or more of the following methods: method for treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy; method for increasing tolerance to dust mites; method for reducing a serum allergen-specific IgE level in a subject; any method of the present invention; method of production of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding claims; any combination of methods as above; and / or any method as above, wherein said method is an in vitro, in vivo or ex vivo method.

[0068] In a further aspect the present invention relates to a use of the nucleic acid construct, polypeptide, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of the present invention for / in one or more of the following: treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy; increasing tolerance to dust mites; reducing a serum allergen-specific IgE level in a subject; any use of the present invention; and / or use in the manufacture of a medicament for any use of the present invention; producing of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of the present invention; any combination of uses of the present invention; and / or any use of the present invention, wherein said use is an in vitro, in vivo or ex vivo use.

[0069] In a further aspect the present invention relates to a RNA construct, comprising or consisting of the following sequences (a), (b), (d) and optionally (c), wherein said sequences are in-frame, preferably in the following order, wherein: (a) a RNA sequence encoding for a signal polypeptide is derived from an N-terminal polypeptidefragment of human or murine LAMP-1 (e.g., having a Uniprot accession number: Q8VH34), preferably the polypeptide fragment is at least 15 amino acids long, further preferably the signal polypeptide has at least 75% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, most preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2; (b) a RNA sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) house dust mite polypeptides, preferably allergens, wherein said polypeptides are selected from the group consisting of (i)-(vi) : (i) a polypeptide having at least 80% (preferably at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 1 house dust mite polypeptide of SEQ ID NO:5 (e.g., SEQ ID NO: 5 is Der p 1 sequence within SEQ ID NO: 676, e.g., as in Figure 1 herein); (ii) a polypeptide having at least 80% (preferably at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der f 1 house dust mite polypeptide of SEQ ID NO: 286 (e.g., SEQ ID NO: 286 is Der f 1 sequence within SEQ ID NO: 677, e.g., as in Figure 1 herein); (iii) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449 (e.g., SEQ ID NO: 449 is Der p 2 sequence within SEQ ID NO: 678, e.g., as in Figure 1 herein); (iv) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Derf 2 house dust mite polypeptide of SEQ ID NO: 535 (e.g., SEQ ID NO: 535 is Der f 2 sequence within SEQ ID NO: 679, e.g., as in Figure 1 herein); (v) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621 (e.g., SEQ ID NO: 621 is Der p 23 sequence within SEQ ID NO: 680, e.g., as in Figure 1 herein); (vi) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NO: 761 (e.g., SEQ ID NO: 761 (DIDHDDDPTTMIDVQTTTVQPSDEFECPTRFGYFADPKDPCKFYICSNWEAIHKSCPGNTRWN EKELTCT) is Der f 23 sequence within SEQ ID NO: 681, e.g., as in Figure 1 herein); (c) optionally, a RNA sequence encoding for one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673; (d) a RNA sequence encoding for, preferably in the following order: (d’)one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; and (d”) one or more cytosolic domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1; preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) have a sequence identity of at least 75% to SEQ ID NO: 674 or SEQ ID NO: 675; further preferably, said one or more transmembrane domains comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.

[0070] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said construct encoding for an enzymatically inactive polypeptide (e.g., according to any construct as shown in Example 4 herein).

[0071] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein the signal polypeptide is derived from an N-terminal polypeptide fragment of human LAMP-1.

[0072] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said RNA construct is suitable for inducing immune tolerance in a subject suffering from house dust mite allergy, suitable for allergen-specific immunotherapy (AIT) and / or for inducing allergen-specific immune tolerance and cross-tolerance against further house dust mite allergens (e.g., referring to the induction of immune tolerance not only to the encoded allergen(s), but also to further allergen species).

[0073] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said construct encoding for one or more (preferably 3 or 6, e.g., (i) Der p 1 (SEQ ID NO: 749), Der p 2 (SEQ ID NO: 753) and Der p 23(SEQ ID NO: 757; or (ii) Der f 1 (SEQ ID NO: 751), Derf 2 (SEQ ID NO: 755), Der f 23 (SEQ ID NO: 759)) polypeptide / s comprising or consisting of polypeptide / s selected from the group consisting of: SEQ ID NOs: 676-681, 749, 751, 753, 755, 757 and 759 (e.g., as shown in Examples 3-4 herein).

[0074] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said RNA molecule is a mRNA molecule, preferably said RNA is a monocistronic or polycistronic mRNA molecule.

[0075] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said nucleic acid comprises one or more modified nucleosides, preferably said one or more modified nucleosides are selected from the group consisting of: m1lP (1-methylpseudouridine); m1acp3lP (1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine); ^Pm (2'-0-methylpseudouridine); m5D (5-methyldihydrouridine); m3^ (3-methylpseudouridine); and / or any combination thereof.

[0076] In a further aspect the present invention relates to the RNA construct of of the present invention, wherein said RNA is engineered or modified to direct the encoded polypeptide to endolysosomal compartments within a cell (e.g., a human cell), preferably, said nucleic acid encodes an endo-lysosomal-targeted polypeptide.

[0077] In a further aspect the present invention relates to an isolated host cell (e.g., isolated recombinant host cell), plurality of said isolated host cells, lipid nanoparticles (LNPs) or polymersomes comprising and / or expressing one or more of the RNA construct / s of any one of the preceding claims.

[0078] In a further aspect the present invention relates to a composition comprising one or more of the RNA construct / s of the present invention, cell / s of the present invention, plurality of cells of the present invention, lipid nanoparticles (LNPs) of the present invention and / or polymersomes of the present invention, preferably said composition is a diagnostic, pharmaceutical composition, immune-therapeutical composition, allergen immunotherapy (AIT) composition, in vitro transcription composition (IVT composition), delivery composition and / or vaccine composition, further preferably said composition is selected from a group consisting: AIT-, IVT- and vaccine composition, most preferably said said composition is a vaccine composition.

[0079] In a further aspect the present invention relates to the composition of the present invention, wherein said composition is a pharmaceutical composition.

[0080] In a further aspect the present invention relates to the RNA construct of the present invention, cell of the present invention, plurality of cells of the present invention, lipid nanoparticles (LNPs) of the present invention, polymersomes of the present invention and / or composition of the present invention, for use as a medicament and / or in therapy.

[0081] In a further aspect the present invention relates to the RNA construct of the present invention, cell of the present invention, plurality of cells of the present invention, lipid nanoparticles (LNPs) of the present invention, polymersomes of the present invention and / or composition of the present invention, for use in one or more of the following methods: (a) method for treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy; (b) method for increasing tolerance to dust mites (preferably in the treatment of house dust mites allergy); (c) method for reducing a serum allergen-specific IgE level in a subject (preferably in the treatment of house dust mites allergy); and / or (d) any combination of methods as in (a)-(c) (preferably in the treatment of house dust mites allergy).BRIEF DESCRIPTION OF THE DRAWINGS

[0082] The invention will be better understood with reference to the detailed description when considered in conjunction with the non-limiting examples and the accompanying drawings, respectively. The Figures show:

[0083] Figure 1 shows a schematic representation and protein sequence of the allergen-LAMP-1 fusion constructs encoded by the exemplary mRNAs of the present invention. Figure 1A: Dermatophagoides pteronyssinus constructs comprising murine LAMP-1 sequence and applied in the presented experiments. The allergen-coding sequences are shown in blue. The signal sequence, as well as the transmembrane domain and the cytosolic domain of LAMP-1 , are shown in red. The connecting Gly-Ser peptide (SEQ ID NO: 673) linker is displayed in gray. Figure 1B: Dermatophagoides pteronyssinus and Dermatophagoides farinae constructs comprising human LAMP-1 sequence and designed to have optimal isoform coverage. Black: allergens; Red: LAMP-1 (the N-terminal part encodes the signal peptide of LAMP-1 and is used to transport the protein into the endosome; the C-terminal part encodes the transmembrane and cytosolic domain of LAMP-1 and is used for transport to the endosome and anchoring in the membrane of the endosome, where colocalization to MHCII takes place); Blue: Propeptide (only illustrated for Der p 1 and Der f 1; can be used for the correct folding of the protein); Grey: Linker.

[0084] Figure 2 shows a schematic representation of the experimental model used for allergenspecific immunotherapy (AIT) of house dust mite allergy. Pipettes and syringes indicate the times of sensitization and provocation or AIT injections, respectively. AIT, allergen-specificimmunotherapy; Der p, Dermatophagoides pteronyssinus; HDM, house dust mite; i.n, intranasal; LNP, lipid nanoparticles; PBS, phosphate-buffered saline; s.c., subcutaneous.

[0085] Figure 3 shows the quantification of the absolute cell counts and numbers of eosinophils, alveolar macrophages, CD4+ lymphocytes, CD8+ lymphocytes and natural killer cells (NK cells) in the bronchoalveolar lavage at the end of the experiment (day 34). The respective cell populations show a significant increase after sensitization and subsequent allergen challenge of the animals without therapy (HDM-allergic) compared to the control group (non-allergic), reflecting a high cell infiltration induced by the allergic inflammation. The applied mRNAAIT of the present invention can significantly reduce the effect of this allergic inflammation by reducing cell infiltration (lower total cell count and reduced cell count of specific effector cells). This contrasts with classic extract AIT, which only leads to a slight reduction in the total cell count and eosinophils. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; BALF, bronchoalveolar lavage; HDM, house dust mite.

[0086] Figure 4 shows the quantification of GATA3+CD4+ T cells (Th2 cells) as a percentage of total CD4+ T cells in lung tissue at the end of the experiment (day 34). Th2 cell-driven allergic inflammation is a central molecular component underlying type 1 allergy (e.g. house dust mite allergy). An increase in this specific T cell population can be seen after allergic sensitization and subsequent provocation. mRNAAIT of the present invention leads to a significant reduction of this disease-associated cell population to a level similar to that observed in the control group (non-allergic). In contrast, extract AIT seems to have no effect. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; HDM, house dust mite.

[0087] Figure 5 shows the level of total (concentration) and house dust mite-specific (OD) IgE antibodies in serum at the end of the experiment (day 34). IgE is considered to be another central molecular component in direct type 1 hyperreactivity reactions. Allergen provocation after previous sensitization leads to a significant increase in allergen-specific IgE in addition to an increase in total IgE in serum. This increase in IgE titer associated with HDM allergy can be significantly reduced by mRNA therapy to the same extent as classical extract AIT. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; Der p, Dermatophagoides pteronyssinus; HDM, house dust mite; OD, optical density.

[0088] Figure 6 shows the level of house dust mite-specific I gG 1 antibodies as well as total I gG1 , lgG2c, lgG2b and lgG3 antibodies in serum at the end of the experiment (day 34). Part of a successful AIT therapy is considered to be the shift from an IgE dominated to a more IgG mediated humoral response. We can observe this type of shift in the course of mRNAAIT. This leads to a significant increase in the p-specific I gG 1 as well as the total I gG 1 and lgG2c titres. This significantincrease is also observed in the course of classic AIT (extract AIT), but to a lesser extent. In addition, only the mRNAAIT leads to a significant reduction in the total lgG3 titer compared to the allergic group (HDM-allergic). Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; Der p, Dermatophagoides pteronyssinus; HDM, house dust mite; OD, optical density.

[0089] Figure 7 shows an amino acid sequence of mature Der p 1 (light blue) and overlapping epitopes of Der p1 specific t cell lines (red bars).

[0090] Figure 8 shows an amino acid sequence of mature Der p 2 (light blue) and overlapping epitopes of Der p 2 specific t cell lines (red bars).

[0091] Figure 9 shows transfection efficiency of HDM mRNA-LNPs in ex-vivo isolated PBMCs from allergic and non-allergic subjects. Expression of Der p / f group 2 via flow cytometry analysis: 106PBMCs per well were treated with 1.0 pg / mL mRNA of trivalent Der p / f 1 / 2 / 23 mRNA-LNPs (LNPA, LNP B) for 24 h. Live / dead staining was conducted with amin-reactive reagent Live / Dead Green (Invitrogen). (A) Transfection efficiency was exemplarily quantified as the frequency of Der p / f 2-positive cells within the HLA-DR+ PBMC population, demonstrating higher efficiencies in APCs compared to the PBS control. (B) Transfection efficiencies in antigen-presenting cell (APC) subsets: Co-staining for HLA-DR with CD14 and CD11c, CD209 as one predominant antigen-presenting cell population exhibiting elevated Der p / f group 2 transfection efficiencies. n=6 independent HDM allergic donors and n=4 non-allergic donors. CD, cluster of differentiation; Der f, Dermatophagoides farinae., Der p, Dermatophagoides pteronyssinus’, HDM, house dust mite; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid.

[0092] Figure 10 shows lnterleukin-5 and Interleukin-13 levels in supernatants of HDM mRNA-LNP treated ex-vivo isolated PBMCs from allergic subjects. Figure 2 shows the level of IL-5 (A, B) and IL-13 (C, D) in supernatants of LNP treated PBMC isolated from allergic (A, C) and non-allergic (B,D) donors measured via Biolegend Legendplex. Notably, supernatants from HDM-allergics showed induction of TH2 cytokines IL-5 and IL-13 indicating an allergen-specific recall response driven by pre-existing memory TH2 cells recognizing the expressed peptide antigen, whereas non-allergic subjects showed negligible or minor cytokine levels. For each donor, two supernatants were measured in independent experiments. HDM, house dust mite; IL, interleukin; LNP, lipid nanoparticle; TH, T helper cell.

[0093] Figure 11 shows the employed experimental model of house dust mite (HDM) induced allergic airway inflammation and allergen-specific immunotherapy (AIT). Female C57BL / 6J mice, 6-8 weeks old, were sensitized with a mixture of Dermatophagoides pteronyssinus (Der p) & Dermatophagoides farinae (Der f) HDM extract (Greer Laboratories Inc.; Der p, Cat#: XPB91D3A2.5, Lot#: 446803; Der f, Cat#:XPB81D3A2.5, Lot#: 435703) by 3 intranasal (i.n.) instillations on 3 consecutive days of 20 pl extract (reconstituted in 0,9% sterile NaCI and dilutedin sterile PBS), 10 pl per nostril, containing a total protein content of 2 pg, 1 pg / species. Non-allergic mice received PBS. On days 7, 12 and 19 mice received further i.n. maintenance challenges as described for the sensitization. On days 14, 17 and 21 mice were treated subcutaneously (s.c.) with 200 pL of either sterile 0,9% NaCI (non-allergic, HDM-allergic) or different LNP preparations (Lipid A - D, variation of the ionizable lipid) with 5 pg mRNA / allergen. Each LNP preparation contained a 50 / 50 mixture of trivalent mRNA-LNPs A & B. Finally, on days 29-32, all mice received i.n. challenges with HDM extract with a total protein content of 10 pg total protein, 5 pg / species. Mice were sacrificed on day 35 for further analysis. AIT, allergen-specific immunotherapy; Der f, Dermatophagoides farinae., Der p, Dermatophagoides pteronyssinus', HDM, house dust mite; i.n., intranasal; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; NaCI, sodium chloride; PBS, phosphate-buffered saline s.c., subcutaneous.

[0094] Figure 12 shows in (A) the quantification of total leukocyte (live CD45+cells) count and the differential cell count of eosinophils (CD11b+CD11c'orlowSiglec-F+Ly6G') in the bronchoalveolar lavage fluid. Cell counts significantly increase after allergic sensitization (HDM-allergic) if compared to non-sensitized mice (non-allergic) reflecting a strong immune cell infiltration after the induction of allergic airway inflammation. mRNA-based allergenimmunotherapy (s.c.) with differently formulated LNPs (Lipid A - D, each formulated with a different ionizable lipid) is able to reduce the observed cell infiltration. In (B) the frequency of TH1 (IFN-Y+FOXP3') and TH2 (GATA3+FOXP3‘) within the T-helper cell population (CD45+CD3+CD4+) is shown. TH2 are slightly elevated after allergic sensitization and represent a major component of type I allergic diseases (e.g. HDM-allergy) and are associated with a type 2 immune response, while mRNA-LNP-based AIT seems to dampen these effects. On the other hand TH1 cells are reduced after sensitization and are significantly increased through mRNA-LNP-based AIT. TH1 cells are associated with a type 1 immune response which is generally discussed as counteracting TH2 biased allergic reactions. Statistical analysis was performed on log-transformed data using either Dunnett’s or Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. Non-allergic and HDM-allergic were compared by Welch’s t-test. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergenspecific immunotherapy; CD, cluster of differentiation; FoxP3, forkhead box P3; GATA3, GATA binding protein 3; HDM, house dust mite; IFN-y, interferon y; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; s.c., subcutaneous; Siglec-F, Sialic acid-binding immunoglobulin-like F; TH, T helper cell.

[0095] Figure 13 shows the titers of different immunoglobulin classes (total) in the serum. Total IgE levels rise through allergic sensitization and stay elevated throughout the course of the mRNA-LNP-based AIT. IgE is another central molecular component of type I hypersensitivity reactions. mRNA-LNP-based AIT leads to significant increases in serum titers of total lgG1, lgG2c, and lgG2b. The shift from an IgE dominated to a IgG mediated humoral response is seen as a major hallmark of a successful AIT. Especially high titers of lgG2c are induced in therapeuticgroups. Data is displayed on logarithmic scale. Statistical analysis was performed on log-transformed data using Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. Non-allergic and HDM-allergic were compared by Welch’s t-test. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergen-specific immunotherapy; HDM, house dust mite; Ig, immunoglobulin; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid.

[0096] Figure 14 shows in (A) the level of allergen-specific lgG1 in the serum, measured as ODA45O values. Measured were lgG1 levels against the group 1 and group 2 HDM allergens of Der p and Derf, as well as Der p 23. Notably, HDM-allergic mice show no induction of allergen-specific lgG1, whereas mRNA-LNP-based AIT leads to significant increases of these levels. In (B) Similarly, a significant induction of allergen-specific lgG2c was observed after mRNA-based AIT against the group 1 and group 2 HDM allergens of Der p and Der f, as well as Der p 23. Taken together this data shows the potency of the mRNA-based AIT to induce potentially protective IgGs. Statistical analysis was performed using Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergen-specific immunotherapy; Der p / f, Dermatophagoides pteronyssinus / farinae', HDM, house dust mite; Ig, immunoglobulin; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; ODA4SO, optical density at 450 nm light wavelength.DETAILED DESCRIPTION OF THE INVENTION

[0097] The present invention is described in detail in the following and is also illustrated by the appended examples and figures.

[0098] As described herein references are made to UniProtKB Accession Numbers (http: / / www.uniprot.org / , e.g., as available in UniProt release 2024_02 published on March 27, 2024).

[0099] As described herein references are made to GeneBank Accession Numbers as available in NCBI-GenBank Release 261.0, published on June 15, 2024.

[0100] Definitions:

[0101] The term “polypeptide" is equally used herein with the term "protein". Proteins (including fragments thereof, preferably biologically active fragments, and peptides, usually having less than 30 amino acids) comprise one or more amino acids coupled to each other via a covalent peptide bond (resulting in a chain of amino acids). The term "polypeptide" as used herein describes a group of molecules, which, for example, consist of more than 30 amino acids. Polypeptides may further form multimers such as dimers, trimers and higher oligomers, i.e. consisting of more than one polypeptide molecule. Polypeptide molecules forming such dimers,trimers etc. may be identical or non-identical. The corresponding higher order structures of such multimers are, consequently, termed homo- or heterodimers, homo- or heterotrimers etc. An example for a heteromultimer is an antibody molecule, which, in its naturally occurring form, consists of two identical light polypeptide chains and two identical heavy polypeptide chains. The terms "polypeptide" and "protein" also refer to naturally modified polypeptides / proteins wherein the modification is effected e.g. by post-translational modifications like glycosylation, acetylation, phosphorylation and the like. Such modifications are well known in the art.

[0102] Sequence identity: The relatedness between two amino acid sequences or between two nucleotide sequences is described by the parameter “sequence identity”. For purposes of the present invention, the sequence identity between two amino acid sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch, 1970, J. Mol. Biol.48: 443-453) as implemented in the Needle program of the EMBOSS package (EMBOSS: The European Molecular Biology Open Software Suite, Rice et al., 2000, Trends Genet. 16: 276-277), preferably version 5.0.0 or later. The parameters used may be gap open penalty of 10, gap extension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix. The output of Needle labeled “longest identity” (obtained using the no-brief option) is used as the percent identity and is calculated as follows:

[0103] (Identical Residues* 100) / (Length of Alignment-Total Number of Gaps in Alignment).

[0104] Alternatively, the parameters used may be gap open penalty of 10, gap extension penalty of 0.5, and the EDNAFULL (EMBOSS version of NCBI NLIC4.4) substitution matrix. The output of Needle labeled “longest identity” (obtained using the no-brief option) is used as the percent identity and is calculated as follows:

[0105] (Identical Deoxyribonucleotides*100) / (Length of Alignment-Total Number of Gaps in Alignment).

[0106] Expression: The term "expression" includes any step involved in the production of a variant (polypeptide) including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion.

[0107] Expression vector: The term "expression vector" may refer to a linear or circular DNA molecule that comprises a nucleic acid construct of the present invention and is operably linked to control sequences that provide for its expression.

[0108] Host cell: The term "host cell" may refer to any cell type that is susceptible to transformation, transfection, transduction, or the like with a nucleic acid construct or expression vector of the present invention. The term "host cell" encompasses any progeny of a parent cell that is not identical to the parent cell due to mutations that occur during replication.

[0109] Nucleic acid construct: The term "nucleic acid construct" may refer to a nucleic acid molecule, either single- or double-stranded, which is isolated from a naturally occurring gene or is modified to contain segments of nucleic acids in a manner that would not otherwise exist in nature or which is synthetic, which may comprise one or more control sequences. Preferably, a nucleic acid construct as used herein (e.g., a RNA or DNA construct) may refer to a synthetic sequence of nucleic acid engineered to achieve a specific biological function when introduced into a cell.

[0110] Operably linked: The term "operably linked" may refer to a configuration in which a control sequence is placed at an appropriate position relative to the coding sequence of a polynucleotide such that the control sequence directs expression of the coding sequence.

[0111] Control sequences: The term "control sequences" as used herein may refer to nucleic acid sequences necessary for expression of a polynucleotide encoding a polypeptide of the present invention. Each control sequence may be native (i.e. , from the same gene) or foreign (i.e., from a different gene) to the polynucleotide encoding the variant or native or foreign to each other. Such control sequences include, but are not limited to, a leader, polyadenylation sequence, propeptide sequence, promoter, signal peptide sequence, and transcription terminator. At a minimum, the control sequences include a promoter, and transcriptional and translational stop signals. The control sequences may be provided with linkers for the purpose of introducing specific restriction sites facilitating ligation of the control sequences with the coding region of the polynucleotide of the present invention.

[0112] As used herein, the terms “nucleic acids” or “nucleotide sequences” may refer to DNA molecules (e.g. cDNA or genomic DNA), RNA (e.g., mRNA), combinations thereof or hybrid molecules comprised of DNA and RNA. The nucleic acids can be double- or single-stranded and may contain double- and single-stranded fragments at the same time.

[0113] The term "nucleic acid sequence encoding" as used herein may refer to a segment of DNA or RNA composed of nucleotides that specify the amino acid sequence of a protein or polypeptide through the process of transcription and translation.

[0114] The term "sequences are in-frame" as used herein may refer to the alignment of a nucleotide sequence in a way that it is correctly divided into consecutive, non-overlapping triplets (codons), which are read during the translation process to produce polypeptides. For proteincoding sequences, being "in-frame" ensures that translation proceeds from the correct starting codon and continues through to a proper stop codon without encountering frame shifts that would alter the intended amino acid sequence of the protein.

[0115] The term “signal polypeptide” as used herein also known as a “signal peptide” or “signal sequence” may refer a short amino acid sequence (e.g., usually 16-30 amino acids long) found at the N-terminus of newly synthesized / translated proteins that are destined for the secretory pathway. These peptides are used to direct the protein to specific locations in the cell,such as the endoplasmic reticulum (ER), from where they can be secreted out of the cell or directed to other specific cellular compartments.

[0116] The term “polypeptide fragment” as used herein may refer to a subsection of a polypeptide chain that consists of a sequence of amino acids shorter than the full-length protein or polypeptide. Preferably, the polypeptide fragment is at least 16 amino acids long, more preferably at least 20 amino acids long, even more preferably at least 24 amino acids long.

[0117] A signal polypeptide may be considered to be “derived from” a polypeptide fragment when having a sequence identity of at least 75% with respect to the polypeptide fragment, while preserving the capability of directing the protein to the specific location in the cell as the polypeptide fragment. So, for example, a signal polypeptide encoded by any one of the nucleic acid constructs of the present invention or included in any one of the polypeptides for AIT of the present invention may be a peptide having at least 75% sequence identity with the first 15, 20, 25, 30, 35, or 40 amino acid residues (e.g., counting from the N-terminus) of murine LAMP-1. Alternatively or in addition, the signal polypeptide may be a peptide having at least 75% sequence identity with the first 15, 20, 25, 30, 35, or 40 amino acid residues (counting from the N-terminus) of human LAMP-1. For example, the signal polypeptide may be a peptide having at least 75% sequence identity to the amino acid residues 1-29 of human LAMP-1, that is, have at least 75% sequence identity to SEQ ID NO:1 and / or a peptide having at least 75 % sequence identity to the amino acid residues 1-24 of murine LAMP-1, that is, have at least 75% sequence identity to SEQ ID NO: 2.

[0118] The term “house dust mite” as used herein may refer to several species of arthropods belonging to the family Pyroglyphidae that commonly inhabit household dust. House dust mites are a significant source of allergens, which are primarily found in their fecal pellets and body fragments. These allergens can trigger allergic reactions, asthma, and other respiratory issues. The most commonly encountered species in homes include Dermatophagoides pteronyssinus, Dermatophagoides farina and Dermatophagoides microceras.

[0119] The term “allergens” as used herein may refer to substances that can trigger an allergic reaction in certain individuals.

[0120] The term “HLA” as used herein may refer to Human Leukocyte Antigen, a complex of genes located on chromosome 6 that play a crucial role in the immune system's function. HLA genes are responsible for the regulation of the immune system in humans. They encode protein molecules located on the surface of cells that are critical for immune function, particularly in the recognition and differentiation between self and non-self molecules. Specific identifiers such as HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; HLA-DRB5*01:01; HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and HLA-DRB5*01:01; HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and HLA-DRB5*01:01 as used herein may refer to specific alleles of the HumanLeukocyte Antigen (HLA) system. These alleles are part of the HLA class II region on chromosome 6, which plays a critical role in the immune system, particularly in managing how the immune system responds to external pathogens and antigens.

[0121] The HLA-binding peptides referred to herein (e.g., above) and in the claims (e.g., the Der p 1-derived HLA-binding peptides having SEQ ID. NOs: 6-283; 682-723; the Der f 1-derived HLA-binding peptides having SEQ ID. NOs 287-448; the Der p 2-derived HLA-binding peptides having SEQ ID. NOs: 450-534; 724-743; the Der f 2-derived HLA-binding peptides having SEQ ID. NOs 536-620; the Der p 23-derived HLA-binding peptides having SEQ ID. NOs:622-647; the Der f 23-derived HLA-binding peptides having SEQ ID. NOs: 649-672) have been determined experimentally, as illustrated in Example 2, or predicted, by using the I ED analysis resource NetMCHIIpan (ver. 4.1), as described in Kaabinejadian S, Barra C, Alvarez B, Yari H, Hildebrand WH, Nielsen M., “Accurate MHC Motif Deconvolution of Immunopeptidomics Data Reveals a Significant Contribution of DRB3, 4 and 5 to the Total DR Immunopeptidome”, 2022, Front Immunol., 13:835454. doi: 10.3389 / fimmu.2022.835454.

[0122] The term “peptide linkers” as used herein may refer to short sequences of amino acids (e.g., 4, 5, 6, 7, 8, 9 or 10) used to connect two proteins or peptides within a larger protein construct.

[0123] The term “transmembrane domains” as used herein may refer to regions or portions within membrane proteins that span the lipid bilayer of cellular membranes. These domains are typically composed of hydrophobic amino acids, which allow the protein to embed stably within the membrane's hydrophobic environment.

[0124] The term “cytosolic domains” as used herein may refer to regions or portions of a protein that are located within the cytosol, the internal fluid of the cell's cytoplasm. These domains are part of larger proteins that may span across or attach to cellular membranes but extend into the cytoplasm.

[0125] The term “enzymatically inactive polypeptide” as used herein may refer to a protein or polypeptide that, while structurally similar to an active enzyme, lacks the ability to catalyze chemical reactions. This inactivity can result from a variety of reasons, including mutations, deletions, or modifications in the amino acid sequence that disrupt the active site or alter the protein's conformation.

[0126] The terms “monocistronic” and “polycistronic” as used herein may refer to the structure and function of mRNA molecules in terms of how many proteins they are capable of encoding. A monocistronic mRNA molecule carries the genetic information to synthesize a single type of protein. This means it has the coding sequence for just one protein. A polycistronic mRNA molecule contains the coding sequences for two or more proteins, typically organized in a series of contiguous open reading frames (ORFs). In a preferred embodiment, a polycistronic mRNA molecule encodes for at least two polypeptides of the present invention. For example, a first one of the encoded polypeptides may include a signal polypeptide, an allergenic domain (sequence(b) above), and a transmembrane and cytosolic domain, as illustrated for any one of the polypeptides in Figure 1. The second encoded polypeptide may also include a signal polypeptide, an allergenic domain (sequence (b), and a transmembrane and cytosolic domain, but may differ from the first polypeptide for encoding a different allergenic domain. For example, the first polypeptide may include, as allergenic domain, a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide according to any one of SEQ ID NO: 3-5, while the second polypeptide may include, as allergenic domain, a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide according to SEQ ID NO: 449. Of course, different combinations of polypeptides are also possible. For example, the first polypeptide may include, as allergenic domain, a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide according to any one of SEQ ID NO: 3-5, while the second peptide may consist of a Derf 1-derived HLA-binding peptide, according to any one of SEQ ID NO 287-448 or of a peptide consisting of a Der p 1-derived HLA binding peptide according to any one of SEQ ID NOs: 682-723. Still further, both polypeptides may be HLA-binding peptides, such as a Der p 2-derived HLA binding peptide according to any one of SEQ ID NOs: 450-531, 724-743, and a Der f 2-derived HLA binding peptide according to any one of SEQ ID NOs: 536-620. Still further, the construct may include for a third polypeptide, differing from the other two also for the allergenic domain. In some embodiments, in addition to the allergenic domain, the polypeptides may differ for including different signal polypeptides and / or transmembrand and / or cytosolic domains. Preferred combination of polypeptides encoded by a polycistronic construct are as given in Table 1A below.

[0127] Table 1A. Preferred combination of polypeptides of the present invention:Allergenic domain Allergenic domain Allergenic domainFirst polypeptide Second polypeptide Third polypeptideDer p 1-derived Der p 2- derived Der p-23 derivedDer f 1 -derived Der f 2 - derived Der f-23 derivedDer p 1 -derived Der f 1 -derivedDer p 2- derived Der f 2- derivedDer p 23- derived Der f 23- derived

[0128] Even more preferred combinations corresponds to the first two lines of the Table 1 above (Der p 1-derived, Der p -2 derived, Der p 23-derived; and Der f 1-derived; Der f 2-derived; Der f 23-derived), and the most preferred combination corresponds to the first line of Table 1 above (see also Example 1 below).

[0129] The term “endo-lysosomal-targeted nucleic acid construct” (e.g., an mRNA molecule) as used herein may refer to a nucleic acid construct (e.g., an mRNA) specifically engineered or modified to direct the encoded protein to endo-lysosomal compartments within a cell.

[0130] The term “lipid nanoparticles (LNPs)” as used herein may refer to synthetic nanoparticles that are made from a mixture of lipids that can encapsulate nucleic acids, protecting them from degradation and facilitating their efficient delivery into target cells. LNPs can typically consist of four main types of lipids: ionizable lipids, which help encapsulate and release the RNA payload within cells; helper lipids, which stabilize the lipid bilayer; cholesterol, which provides structural integrity; and polyethylene glycol (PEG)-modified lipids, which help extend circulation time in the body by evading the immune system. Exemplary LNPs can be formulated as follows: 40-60 mol% ionizable lipid (preferably 50 mol%) 36.5-38.5 mol% cholesterol (preferably 37.5 mol%), 9-10 mol% (preferably 10 mol%), DSPC, and 1.5-3.5 mol% PEG-lipid (pereferably 2.5 mol%).

[0131] The term “polymersomes” as used herein may refer to are synthetic vesicles formed from amphiphilic block copolymers.

[0132] The term “IgE” as used herein may refer to Immunoglobulin E, which is a class of antibodies found in mammals that plays a critical role in the body’s allergic responses and defense against parasitic infections. It is one of the five main types of immunoglobulins (antibodies) produced by the immune system.

[0133] The term “kU / L” or kilo units per liter, as used herein may refer to a unit of measurement commonly used in medical diagnostics to quantify the concentration of substances in blood or other bodily fluids. Specifically, it is often used to measure the concentration of antibodies, such as Immunoglobulin E (IgE), in allergy testing.

[0134] In one aspect, the present invention relates to endo-lysosomal-targeted nucleic acid constructs encoding one or more HDM allergens (e.g., at least three allergens) and endo-lysosomal-targeting polypeptides as well as methods and uses thereof, particularly in desensitization- and therapeutical methods relating to HDM-caused allergies.

[0135] The present invention particularly relates to mRNA therapy based on the endo-lysosomal-targeted nucleic acid constructs of the present invention encoding one or more HDM allergens, which is particularly well-tolerated and effective.

[0136] Additionally, endo-lysosomal-targeted nucleic acid constructs of the present invention (e.g., mRNAs) can have an immunostimulatory effect, particularly when N1-methylpseudouridine is used, deviating from a natural mRNA.

[0137] In a further aspect of the present invention, this stimulation leads to enhanced antigen presentation and typically promotes a Type-1 immune response (e.g., IFN-mediated), which counteracts the allergic Type-2 response.

[0138] In a further aspect of the present invention, a faster tolerogenic maturation of T cells takes place due to the reduced availability of allergens in circulation, as initially less IgE is produced. In classic immunotherapy, particularly in the first year of treatment, an increase in IgE is observed, which may prolong the therapy. Beyond these mechanistic aspects, production is also faster and much more cost-effective. Overall, mRNA-based allergen-specific immunotherapy of the present invention provides an opportunity to clearly define the allergen composition of the therapeutic agent, ensuring the therapeutic does not suffer quality variations due to the natural variability of the raw materials and contains no substances that could potentially reduce the effectiveness of the therapy. This has significant potential to increase the efficacy of AIT. The reproducible and simple manufacturability not only offers advantages over extraction from natural allergen sources, but also over the costly production of recombinant allergens.

[0139] In a further aspect of the present invention, it is possible to specifically induce tolerogenic immune responses, which can further enhance the effectiveness of AIT. This approach also allows for the release of intact allergens from cells and avoids activating allergy-triggering mechanisms, thereby increasing the safety of AIT.

[0140] In a further aspect of the present invention, there is a wide range of options, such as the use of lipid nanoparticles or polymersomes for specific targeting of cells or immunomodulators that make the allergen even more tolerogenic.

[0141] In some preferred aspects of the present invention, in order to enhance both safety and / or specificity of desensitization, not all 32 described house dust mite allergens are employed. Instead, a subset of polypeptides (which may include endo-lysosomal targeted wild-type allergens, derivatives thereform, or allergenic sequences derived from the native allergens) may be advantageously used. Specifically, a composition may be provided in which one or more nucleic acid constructs encode for polypeptides differing from each other for one or more of the signal polypeptide / s, the allergenic domain / s (the sequence (b) described above), and / or the transmembrane and / or cytosolic domain / s. Preferably, the polypeptides differ from each other at least for the allergenic domain / s. The number of different polypeptides is not limited. Preferably, at least three different polypeptides are encoded.

[0142] One or more of the nucleic acid constructs included may be polycistronic -encoding for at least two polypeptides - or multiple monocistronic nucleic acid constructs may be included, each encoding a respective polypeptide. Mixtures of monocistronic and polycistronic nucleic acid constructs are also possible.

[0143] The encoded polypeptides will generally include at least an allergenic domain. In some preferred embodiments, the allergenic domains encoded by the polypeptides may be derived from a selected subset of house dust mite allergens. For example, a first polypeptide may comprise or consist of the one or more Der p 1-derived HLA-binding peptides described below, and a second polypeptide may comprise or consist of the one or more Der p-2 derivedH LA-binding peptides described below; furthermore, a third polypeptide may comprise or consists of the one or more Der p-23 derived H LA-binding peptides described below. Each one of the first polypeptide, the second polypeptide and the third polypeptide may independently be a peptide consisting of an HLA binding peptide, may comprise more than one HLA binding peptides, and / or may be a polypeptide further comprising one or more of the signal polypeptides, the transmembrane domain(s), and / or the cytosolic domain(s). Preferred combinations of the allergenic domains (sequence b) are indicated in the Table 1B below.

[0144] Table 1B. Preferred combinations of the allergenic domains of the present invention.Allergenic domain Allergenic domain Allergenic domainFirst polypeptide Second polypeptide Third polypeptideDer p 1 -derived Der p 2- derived Der p-23 derivedDer f 1 -derived Der f 2 - derived Der f-23 derivedDer p 1 -derived Der f 1 -derivedDer p 2- derived Der f 2- derivedDer p 23- derived Der f 23- derivedDer p 1 -derived Der p 1- derived Der p 1- derivedDer p 2-derived Der p 2- derived Der p 2- derivedDer p 23-derived Der p 23- derived Der p 23- derivedDer p 1 -derived Der p 1- derived Derf-1 derivedDer p 1 -derived Der p 2 derived Derf-1 derived

[0145] Most preferably, only three principal house dust mite allergens, specifically Der p 1, Der p 2 und Der p 23, are advantageously used as described elsewhere herein (e.g., as depicted in Example 1 (e.g., Figure 1) and / or 2 and / or Example 3 and / or Example 4 herein, e.g., Table 1A, Table 1B, Table 2 and / or 3). Those are the most preferred allergens of the present invention.

[0146] In some other aspects of the present invention, polypeptide sequences of HDM allergens of the present invention are fused with a polypeptide signal sequence, as well as the transmembrane and cytosolic domains of LAMP-1 (Lysosome-associated membrane glycoprotein 1) or other suitable alternative domains as disclosed elsewhere herein. This fusion directs the allergens into endo-lysosomal compartments within the cell, where they colocalize with MHC class II molecules. This colocalization aims to enhance the crucial antigen-presentation process.

[0147] In some further aspects of the present invention, a high dose of antigen is used for inducing a regulatory T-cell response. Additionally, this mechanism advantageously prevents large quantities of allergens from being freely available in the body, potentially minimizing side effects of the therapy.

[0148] In some additional aspects of the present invention, mRNA-based, endo-lysosomal-focused means of the present invention (e.g., constructs and polypeptides) and methods (e.g., immunotherapy) based thereon advantageously do not trigger a B-cell response. Particularly, lgG4 produced by B cells is considered an important mechanism of action. Preferably, polypeptides of the present invention (e.g., allergens) are released in a 3D structure only from dying cells, which may themselves have an anti-inflammatory effect and thus limit adverse reactions. The constructs of the present invention (e.g., mRNAs of the present invention) can advantageously be taken up by the cells encapsulated in lipid nanoparticles (LNP) or polymersomes and not trigger a B-cell response.

[0149] The present invention further relates to the following items:1. A nucleic acid construct (e.g., selected from RNA and / or DNA constructs) comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the following sequences, preferably fused in-frame, further preferably in the following order:a) a nucleic acid sequence encoding for a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1, further preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 (MAAPGSARRPLLLLLLLLLLGLMHCASA) and / or the murine SEQ ID NO: 2 (MAAPGARRPLLLLLLAGLAHGASA);b) a nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more, preferably 3, e.g., as depicted in Example 1 (e.g., as depicted in Figure 1) and / or Example 2 and / or Example 3 and / or Example 4 herein, e.g., as depicted in Table 2 and / or 3 herein) house dust mite polypeptides (e.g., allergens), preferably selected from the group consisting of or comprising one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the following polypeptides: i) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Derp l house dust mite polypeptide (e.g., Derp l Isoform 0102) selected from the group consisting of: (a’)-(c’), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA- DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01 :01 ; and / or HLA-DRB5*01 :01 :a’) SEQ ID NO: 5(RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAETNACSINGN APAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAATESAYLAYRN QSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNGVVQESYYRY VAREQSCRRPNAQRFGISNYCQIYPPNVNKIREALAQTHSAIAVII GIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYW IVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVIL); b’) SEQ ID NO: 4 (RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAE); and c) SEQ ID NO: 3 (TNACSINGNAPAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAAT ESAYLAYRNQSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNG VVQESYYRYVAREQSCRRPNAQRFGISNYCQIYPPNVNKIREAL AQTHSAIAVIIGIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGY SNAQGVDYWIVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYW IL);ii) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 1-derived HLA-binding peptides (as depicted in Table 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA- DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01 :01 ; and / or HLA-DRB5*01 :01 ; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NO: 6 HAVNIVGYSNAQGVDSEQ ID NO: 7 AVNIVGYSNAQGVDYSEQ ID NO: 8 YHAVNIVGYSNAQGVSEQ ID NO: 9 VNIVGYSNAQGVDYWSEQ ID NO: 10 ESVKYVQSNGGAINHSEQ ID NO: 11 SVKYVQSNGGAINHLSEQ ID NO: 12 LESVKYVQSNGGAINSEQ ID NO: 13 SYATFEDEEAARKNFSEQ ID NO: 14 YATFEDEEAARKNFLSEQ ID NO: 15 YLAYRNQSLDLAEQESEQ ID NO: 16 AYLAYRNQSLDLAEQSEQ ID NO: 17 LAYRNQSLDLAEQELSEQ ID NO: 18 FSGVAATESAYLAYRSEQ ID NO: 19 KSYATFEDEEAARKN SEQ ID NO: 20 DNGYQPNYHAVNIVG SEQ ID NO: 21 DLSLDEFKNRFLMSA SEQ ID NO: 22 RDNGYQPNYHAVNIV SEQ ID NO: 23 ESAYLAYRNQSLDLA SEQ ID NO: 24 SAYLAYRNQSLDLAE SEQ ID NO: 25 AFSGVAATESAYLAY SEQ ID NO: 26 ATFEDEEAARKNFLE SEQ ID NO: 27 TESAYLAYRNQSLDL SEQ ID NO: 28 SVKYVQSNGGAINHL SEQ ID NO: 29 IREALAQTHSAIAVI SEQ ID NO: 30 VKYVQSNGGAINHLS SEQ ID NO: 31 VKYVQSNGGAINHLS SEQ ID NO: 32 ESVKYVQSNGGAINH SEQ ID NO: 33 ATESAYLAYRNQSLD SEQ ID NO: 34 QRDNGYQPNYHAVNI SEQ ID NO: 35 SDLSLDEFKNRFLMS SEQ ID NO: 36 LDAFRHYDGRTIIQR SEQ ID NO: 37 PRGIEYIQHNGVVQE SEQ ID NO: 38 NIVGYSNAQGVDYWI SEQ ID NO: 39 KIREALAQTHSAIAV SEQ ID NO: 40 NYHAVNIVGYSNAQG SEQ ID NO: 41 WAFSGVAATESAYLA SEQ ID NO: 42 REALAQTHSAIAVII SEQ ID NO: 43 SGVAATESAYLAYRN SEQ ID NO: 44 FLESVKYVQSNGGAI SEQ ID NO: 45 FEHLKTQFDLNAETN SEQ ID NO: 46 NGYQPNYHAVNIVGY SEQ ID NO: 47 DLDAFRHYDGRTIIQ SEQ ID NO: 48 PSSIKTFEEYKKAFN SEQ ID NO: 49 IPRGIEYIQHNGWQ SEQ ID NO: 50 DAFRHYDGRTIIQRD SEQ ID NO: 51 AVNIVGYSNAQGVDY SEQ ID NO: 52 ACSINGNAPAEIDLR SEQ ID NO: 53 LESVKYVQSNGGAIN SEQ ID NO: 54 SAYLAYRNQSLDLAE SEQ ID NO: 55 PRGIEYIQHNGVVQESEQ ID NO: 56 YGYFAANIDLMMIEE SEQ ID NO: 57 RPSSIKTFEEYKKAF SEQ ID NO: 58 KKAFNKSYATFEDEE SEQ ID NO: 59 QPNYHAVNIVGYSNA SEQ ID NO: 60 NAPAEIDLRQMRTVT SEQ ID NO: 61 KTQFDLNAETNACSI SEQ ID NO: 62 AYRNQSLDLAEQELV SEQ ID NO: 63 LKTQFDLNAETNACS SEQ ID NO: 64 GNAPAEIDLRQMRTV SEQ ID NO: 65 PRGIEYIQHNGVVQE SEQ ID NO: 66 VNIVGYSNAQGVDYW SEQ ID NO: 67 YQPNYHAVNIVGYSN SEQ ID NO: 68 GGAINHLSDLSLDEF SEQ ID NO: 69 HAVNIVGYSNAQGVD SEQ ID NO: 70 LESVKYVQSNGGAIN SEQ ID NO: 71 NGGAINHLSDLSLDE SEQ ID NO: 72 LSDLSLDEFKNRFLM SEQ ID NO: 73 GYGYFAANIDLMMIE SEQ ID NO: 74 KYVQSNGGAINHLSD SEQ ID NO: 75 AFEHLKTQFDLNAET SEQ ID NO: 76 NKSYATFEDEEAARK SEQ ID NO: 77 GIEYIQHNGWQESY SEQ ID NO: 78 QPNYHAVNIVGYSNA SEQ ID NO: 79 LSLDEFKNRFLMSAE SEQ ID NO: 80 NKSYATFEDEEAARK SEQ ID NO: 81 KDLDAFRHYDGRTII SEQ ID NO: 82 YKKAFNKSYATFEDE SEQ ID NO: 83 FLESVKYVQSNGGAI SEQ ID NO: 84 IPRGIEYIQHNGVVQ SEQ ID NO: 85 IEYIQHNGVVQESYY SEQ ID NO: 86 NACSINGNAPAEIDL SEQ ID NO: 87 RTIIQRDNGYQPNYH SEQ ID NO: 88 EHLKTQFDLNAETNA SEQ ID NO: 89 NGNAPAEIDLRQMRT SEQ ID NO: 90 RGIEYIQHNGVVQES SEQ ID NO: 91 LRQMRTVTPIRMQGG SEQ ID NO: 92 RGIEYIQHNGVVQESSEQ ID NO: 93 IQRDNGYQPNYHAVN SEQ ID NO: 94 IAVIIGIKDLDAFRH SEQ ID NO: 95 IAVIIGIKDLDAFRH SEQ ID NO: 96 ESAYLAYRNQSLDLA SEQ ID NO: 97 GRTIIQRDNGYQPNY SEQ ID NO: 98 TIPRGIEYIQHNGVV SEQ ID NO: 99 GYFAANIDLMMIEEY SEQ ID NO: 100 IPRGIEYIQHNGWQ SEQ ID NO: 101 LDAFRHYDGRTIIQR SEQ ID NO: 102 NKIREALAQTHSAIA SEQ ID NO: 103 RGIEYIQHNGVVQES SEQ ID NO: 104 TNACSINGNAPAEID SEQ ID NO: 105 GYQPNYHAVNIVGYS SEQ ID NO: 106 PRGIEYIQHNGVVQE SEQ ID NO: 107 ESVKYVQSNGGAINH SEQ ID NO: 108 PRGIEYIQHNGVVQE SEQ ID NO: 109 RTIIQRDNGYQPNYH SEQ ID NO: 110 TESAYLAYRNQSLDL SEQ ID NO: 111 ATESAYLAYRNQSLD SEQ ID NO: 112 DLRQMRTVTPIRMQG SEQ ID NO: 113 ESVKYVQSNGGAINH SEQ ID NO: 114 ESVKYVQSNGGAINH SEQ ID NO: 115 TFEEYKKAFNKSYAT SEQ ID NO: 116 YQPNYHAVNIVGYSN SEQ ID NO: 117 DGRTIIQRDNGYQPN SEQ ID NO: 118 FNKSYATFEDEEAAR SEQ ID NO: 119 QGVDYWIVRNSWDTN SEQ ID NO: 120 SVKYVQSNGGAINHL SEQ ID NO: 121 FEEYKKAFNKSYATF SEQ ID NO: 122 TIPRGIEYIQHNGVV SEQ ID NO: 123 DLDAFRHYDGRTIIQ SEQ ID NO: 124 AIAVIIGIKDLDAFR SEQ ID NO: 125 AIAVIIGIKDLDAFR SEQ ID NO: 126 SSIKTFEEYKKAFNK SEQ ID NO: 127 GRTIIQRDNGYQPNY SEQ ID NO: 128 GIEYIQHNGVVQESY SEQ ID NO: 129 QPNYHAVNIVGYSNASEQ ID NO: 130 NKSYATFEDEEAARK SEQ ID NO: 131 NKSYATFEDEEAARK SEQ ID NO: 132 GDNGYGYFAANIDLM SEQ ID NO: 133 NKSYATFEDEEAARK SEQ ID NO: 134 QPNYHAVNIVGYSNA SEQ ID NO: 135 CSINGNAPAEIDLRQ SEQ ID NO: 136 INHLSDLSLDEFKNR SEQ ID NO: 137 SVKYVQSNGGAINHL SEQ ID NO: 138 IKDLDAFRHYDGRTI SEQ ID NO: 139 PRGIEYIQHNGVVQE SEQ ID NO: 140 AVIIGIKDLDAFRHY SEQ ID NO: 141 RGIEYIQHNGVVQES SEQ ID NO: 142 QESYYRYVAREQSCR SEQ ID NO: 143 EYKKAFNKSYATFED SEQ ID NO: 144 PRGIEYIQHNGVVQE SEQ ID NO: 145 APAEIDLRQMRTVTP SEQ ID NO: 146 EALAQTHSAIAVIIG SEQ ID NO: 147 YQPNYHAVNIVGYSN SEQ ID NO: 148 HLKTQFDLNAETNAC SEQ ID NO: 149 EAFEHLKTQFDLNAE SEQ ID NO: 150 NFLESVKYVQSNGGA SEQ ID NO: 151 DNGYGYFAANIDLMM SEQ ID NO: 152 LESVKYVQSNGGAIN SEQ ID NO: 153 YGYFAANIDLMMIEE SEQ ID NO: 154 PSSIKTFEEYKKAFN SEQ ID NO: 155 GIEYIQHNGVVQESY SEQ ID NO: 156 QESYYRYVAREQSCR SEQ ID NO: 157 AATESAYLAYRNQSL SEQ ID NO: 158 KKAFNKSYATFEDEE SEQ ID NO: 159 NGYGYFAANIDLMMI SEQ ID NO: 160 WGDNGYGYFAANIDL SEQ ID NO: 161 LESVKYVQSNGGAIN SEQ ID NO: 162 VVQESYYRYVAREQS SEQ ID NO: 163 ESAYLAYRNQSLDLA SEQ ID NO: 164 LESVKYVQSNGGAIN SEQ ID NO: 165 GVDYWIVRNSWDTNW SEQ ID NO: 166 RQMRTVTPIRMQGGCSEQ ID NO: 167 GYGYFAANIDLMMIE SEQ ID NO: 168 IIGIKDLDAFRHYDG SEQ ID NO: 169 AEAFEHLKTQFDLNA SEQ ID NO: 170 IPRGIEYIQHNGWQ SEQ ID NO: 171 NIVGYSNAQGVDYWI SEQ ID NO: 172 CWAFSGVAATESAYL SEQ ID NO: 173 PNYHAVNIVGYSNAQ SEQ ID NO: 174 DAFRHYDGRTIIQRD SEQ ID NO: 175 AEAFEHLKTQFDLNA SEQ ID NO: 176 IDLRQMRTVTPIRMQ SEQ ID NO: 177 DGRTIIQRDNGYQPN SEQ ID NO: 178 FNKSYATFEDEEAAR SEQ ID NO: 179 FNKSYATFEDEEAAR SEQ ID NO: 180 TFEEYKKAFNKSYAT SEQ ID NO: 181 GYQPNYHAVNIVGYS SEQ ID NO: 182 YQPNYHAVNIVGYSN SEQ ID NO: 183 VVQESYYRYVAREQS SEQ ID NO: 184 ESYYRYVAREQSCRR SEQ ID NO: 185 KTFEEYKKAFNKSYA SEQ ID NO: 186 SNGGAINHLSDLSLD SEQ ID NO: 187 IPRGIEYIQHNGWQ SEQ ID NO: 188 ESAYLAYRNQSLDLA SEQ ID NO: 189 YRYVAREQSCRRPNA SEQ ID NO: 190 IPRGIEYIQHNGWQ SEQ ID NO: 191 AVNIVGYSNAQGVDY SEQ ID NO: 192 DGRTIIQRDNGYQPN SEQ ID NO: 193 VQESYYRYVAREQSC SEQ ID NO: 194 KSYATFEDEEAARKN SEQ ID NO: 195 EYIQHNGWQESYYR SEQ ID NO: 196 FNKSYATFEDEEAAR SEQ ID NO: 197 FNKSYATFEDEEAAR SEQ ID NO: 198 YYRYVAREQSCRRPN SEQ ID NO: 199 IPRGIEYIQHNGWQ SEQ ID NO: 200 GRTIIQRDNGYQPNY SEQ ID NO: 201 KSYATFEDEEAARKN SEQ ID NO: 202 GIKDLDAFRHYDGRT SEQ ID NO: 203 SAEAFEHLKTQFDLNSEQ ID NO: 204 KAFNKSYATFEDEEA SEQ ID NO: 205 RNSWDTNWGDNGYGY SEQ ID NO: 206 LDAFRHYDGRTIIQR SEQ ID NO: 207 AVIIGIKDLDAFRHY SEQ ID NO: 208 PPNVNKIREALAQTH SEQ ID NO: 209 AQGVDYWIVRNSWDT SEQ ID NO: 210 TIPRGIEYIQHNGVV SEQ ID NO: 211 LRQMRTVTPIRMQGG SEQ ID NO: 212 FEEYKKAFNKSYATF SEQ ID NO: 213 ESYYRYVAREQSCRR SEQ ID NO: 214 KDLDAFRHYDGRTII SEQ ID NO: 215 NKSYATFEDEEAARK SEQ ID NO: 216 RGIEYIQHNGVVQES SEQ ID NO: 217 VNKIREALAQTHSAI SEQ ID NO: 218 RPSSIKTFEEYKKAF SEQ ID NO: 219 EEYKKAFNKSYATFE SEQ ID NO: 220 GYQPNYHAVNIVGYS SEQ ID NO: 221 NVNKIREALAQTHSA SEQ ID NO: 222 NFLESVKYVQSNGGA SEQ ID NO: 223 YKKAFNKSYATFEDE SEQ ID NO: 224 NGYGYFAANIDLMMI SEQ ID NO: 225 AINHLSDLSLDEFKN SEQ ID NO: 226 DGRTIIQRDNGYQPN SEQ ID NO: 227 TIIQRDNGYQPNYHA SEQ ID NO: 228 HAVNIVGYSNAQGVD SEQ ID NO: 229 KSYATFEDEEAARKN SEQ ID NO: 230 VIIGIKDLDAFRHYD SEQ ID NO: 231 GYQPNYHAVNIVGYS SEQ ID NO: 232 LRQMRTVTPIRMQGG SEQ ID NO: 233 SAEAFEHLKTQFDLN SEQ ID NO: 234 VQESYYRYVAREQSC SEQ ID NO: 235 RGIEYIQHNGVVQES SEQ ID NO: 236 SINGNAPAEIDLRQM SEQ ID NO: 237 VRNSWDTNWGDNGYG SEQ ID NO: 238 FLESVKYVQSNGGAI SEQ ID NO: 239 TESAYLAYRNQSLDL SEQ ID NO: 240 KTFEEYKKAFNKSYASEQ ID NO: 241 PNYHAVNIVGYSNAQ SEQ ID NO: 242 TIIQRDNGYQPNYHA SEQ ID NO: 243 TIPRGIEYIQHNGVV SEQ ID NO: 244 GAINHLSDLSLDEFK SEQ ID NO: 245 KYVQSNGGAINHLSD SEQ ID NO: 246 AFNKSYATFEDEEAA SEQ ID NO: 247 AEAFEHLKTQFDLNA SEQ ID NO: 248 AYLAYRNQSLDLAEQ SEQ ID NO: 249 NGYQPNYHAVNIVGY SEQ ID NO: 250 YHAVNIVGYSNAQGV SEQ ID NO: 251 QESYYRYVAREQSCR SEQ ID NO: 252 AFNKSYATFEDEEAA SEQ ID NO: 253 FSGVAATESAYLAYR SEQ ID NO: 254 GYFAANIDLMMIEEY SEQ ID NO: 255 EYKKAFNKSYATFED SEQ ID NO: 256 VIIGIKDLDAFRHYD SEQ ID NO: 257 DAFRHYDGRTIIQRD SEQ ID NO: 258 HSAIAVIIGIKDLDA SEQ ID NO: 259 YDGRTIIQRDNGYQP SEQ ID NO: 260 ATESAYLAYRNQSLD SEQ ID NO: 261 SYYRYVAREQSCRRP SEQ ID NO: 262 SYATFEDEEAARKNF SEQ ID NO: 263 AFRHYDGRTIIQRDN SEQ ID NO: 264 AFNKSYATFEDEEAA SEQ ID NO: 265 VNIVGYSNAQGVDYW SEQ ID NO: 266 YRYVAREQSCRRPNA SEQ ID NO: 267 INGNAPAEIDLRQMR SEQ ID NO: 268 DTIPRGIEYIQHNGV SEQ ID NO: 269 EHLKTQFDLNAETNA SEQ ID NO: 270 GRTIIQRDNGYQPNY SEQ ID NO: 271 KNRFLMSAEAFEHLK SEQ ID NO: 272 PNYHAVNIVGYSNAQ SEQ ID NO: 273 QGVDYWIVRNSWDTN SEQ ID NO: 274 IIGIKDLDAFRHYDG SEQ ID NO: 275 GIEYIQHNGVVQESY SEQ ID NO: 276 SAYLAYRNQSLDLAE SEQ ID NO: 277 NWGDNGYGYFAANIDSEQ ID NO: 278 ACSINGNAPAEIDLRSEQ ID NO: 279 VKYVQSNGGAINHLS SEQ ID NO: 280 DNGYGYFAANIDLMM SEQ ID NO: 281 AVNIVGYSNAQGVDY SEQ ID NO: 282 YPPNVNKIREALAQT SEQ ID NO: 283 KSYATFEDEEAARKNSEQ ID NO: 682 TNACSINGNAPSEQ ID NO: 683 TNACSINGNAPASEQ ID NO: 684 APAEIDLRQMRTSEQ ID NO: 685 EIDLRQMRTVTPSEQ ID NO: 686 EIDLRQMRTVTPISEQ ID NO: 687 LRQMRTVTPIRMSEQ ID NO: 688 MRTVTPIRMQGGSEQ ID NO: 689 VTPIRMQGGCSEQ ID NO: 690 QGGCGSCWAFSGSEQ ID NO: 691 QGGCGSCWAFSGVAATES SEQ ID NO: 692 CWAFSGVAATESSEQ ID NO: 693 VAATESAYLAYRSEQ ID NO: 694 NQSLDLAEQELVDCA SEQ ID NO: 695 NQSLDLAEQELVDCA SEQ ID NO: 696 GIEYIQHNGWQESY SEQ ID NO: 697 YIQHNGVVQESYSEQ ID NO: 698 HNGVVQESYYRYSEQ ID NO: 699 HNGVVQESYYRYVAR SEQ ID NO: 700 VVQESYYRYVARSEQ ID NO: 701 ESYYRYVAREQSSEQ ID NO: 702 PNAQRFGISNYCQIYPPN SEQ ID NO: 703 QRFGISNYCQIYPPN SEQ ID NO: 704 NYCQIYPPNVNKSEQ ID NO: 705 PNVNKIREALAQTHSEQ ID NO: 706 VNKIREALAQTHSAIA SEQ ID NO: 707 ALAQTHSAIAVIIGIKSEQ ID NO: 708 AVIIGIKDLDAFSEQ ID NO: 709 KDLDAFRHYDGRSEQ ID NO: 710 KDLDAFRHYDGRTIISEQ ID NO: 711 DAFRHYDGRTIIQSEQ ID NO: 712 RHYDGRTIIQRDNGYQPNSEQ ID NO: 713 RHYDGRTIIQRDSEQ ID NO: 714 TIIQRDNGYQPNSEQ ID NO: 715 NGYQPNYHAVNISEQ ID NO: 716 QPNYHAVNIVGYSNAQGVDYWSEQ ID NO: 717 YHAVNIVGYSNAQGVSEQ ID NO: 718 VNIVGYSNAQGVSEQ ID NO: 719 VNIVGYSNAQGVDYWSEQ ID NO: 720 VNIVGYSNAQGVDSEQ ID NO: 721 VGYSNAQGVDYWIVRSEQ ID NO: 722 NGYGYFAANIDLMSEQ ID NO: 723 DLMMIEEYPYViii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Der f 1 house dust mite polypeptide (e.g., Der f 1 Isoform 0101), preferably selected from the group consisting of: (a”)-(c”), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a”) SEQ ID NO: 284 (TSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAA TESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQN GWEERSYPYVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREA LTQTHTAIAVIIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVG YGSTQGVDYWI VRNSWDTTWG DSGYGYFQAGN N LMM I EQYPY VVIM);b”) SEQ ID NO: 285 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAE); and c”) SEQ ID NO: 286 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAETSACRINSV NVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAATESAYLAYR NTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQNGWEERSYP YVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREALTQTHTAIAVIIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDY Wl VR N SWDTTWG DSG YG YFQAG N N LM M I EQYPYVVI M) ; iv) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 1 -derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1 -derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 287 AVNIVGYGSTQGVDYSEQ ID NO: 288 HAVNIVGYGSTQGVDSEQ ID NO: 289 VNIVGYGSTQGVDYWSEQ ID NO: 290 YHAVNIVGYGSTQGVSEQ ID NO: 291 FSGVAATESAYLAYRSEQ ID NO: 292 DNGYQPNYHAVNIVGSEQ ID NO: 293 HDNGYQPNYHAVNIVSEQ ID NO: 294 PRGIEYIQQNGVVEESEQ ID NO: 295 PRGIEYIQQNGVVEESEQ ID NO: 296 AFSGVAATESAYLAYSEQ ID NO: 297 QHDNGYQPNYHAVNISEQ ID NO: 298 ESAYLAYRNTSLDLSSEQ ID NO: 299 IPRGIEYIQQNGWESEQ ID NO: 300 IPRGIEYIQQNGWESEQ ID NO: 301 WAFSGVAATESAYLASEQ ID NO: 302 SGVAATESAYLAYRNSEQ ID NO: 303 TESAYLAYRNTSLDLSEQ ID NO: 304 NGYQPNYHAVNIVGYSEQ ID NO: 305 LRAFQHYDGRTIIQHSEQ ID NO: 306 ATESAYLAYRNTSLDSEQ ID NO: 307 GRTIIQHDNGYQPNYSEQ ID NO: 308 DLRAFQHYDGRTIIQSEQ ID NO: 309 IAVIIGIKDLRAFQHSEQ ID NO: 310 YLAYRNTSLDLSEQESEQ ID NO: 311 TIPRGIEYIQQNGWSEQ ID NO: 312 QPNYHAVNIVGYGSTSEQ ID NO: 313 GIEYIQQNGWEERSSEQ ID NO: 314 RAFQHYDGRTIIQHDSEQ ID NO: 315 DGRTIIQHDNGYQPN SEQ ID NO: 316 IKDLRAFQHYDGRTI SEQ ID NO: 317 GIKDLRAFQHYDGRT SEQ ID NO: 318 RGIEYIQQNGVVEER SEQ ID NO: 319 TIPRGIEYIQQNGVV SEQ ID NO: 320 KDLRAFQHYDGRTII SEQ ID NO: 321 YQPNYHAVNIVGYGS SEQ ID NO: 322 IEYIQQNGVVEERSY SEQ ID NO: 323 AIAVIIGIKDLRAFQ SEQ ID NO: 324 NIVGYGSTQGVDYWI SEQ ID NO: 325 RTIIQHDNGYQPNYH SEQ ID NO: 326 PRGIEYIQQNGVVEE SEQ ID NO: 327 LRSLRTVTPIRMQGG SEQ ID NO: 328 IAVIIGIKDLRAFQH SEQ ID NO: 329 SAYLAYRNTSLDLSE SEQ ID NO: 330 RGIEYIQQNGVVEER SEQ ID NO: 331 GRTIIQHDNGYQPNY SEQ ID NO: 332 AYLAYRNTSLDLSEQ SEQ ID NO: 333 QPNYHAVNIVGYGST SEQ ID NO: 334 IQHDNGYQPNYHAVN SEQ ID NO: 335 RGIEYIQQNGVVEER SEQ ID NO: 336 GYQPNYHAVNIVGYG SEQ ID NO: 337 QNGVVEERSYPYVAR SEQ ID NO: 338 QNGVVEERSYPYVAR SEQ ID NO: 339 NYHAVNIVGYGSTQG SEQ ID NO: 340 IREALTQTHTAIAVI SEQ ID NO: 341 DLRSLRTVTPIRMQG SEQ ID NO: 342 LAYRNTSLDLSEQEL SEQ ID NO: 343 QNGVVEERSYPYVAR SEQ ID NO: 344 DGRTIIQHDNGYQPN SEQ ID NO: 345 IGIKDLRAFQHYDGR SEQ ID NO: 346 AIAVIIGIKDLRAFQ SEQ ID NO: 347 REALTQTHTAIAVII SEQ ID NO: 348 DGRTIIQHDNGYQPN SEQ ID NO: 349 AVIIGIKDLRAFQHY SEQ ID NO: 350 LRAFQHYDGRTIIQH SEQ ID NO: 351 AIAVIIGIKDLRAFQSEQ ID NO: 352 YQPNYHAVNIVGYGS SEQ ID NO: 353 QQNGVVEERSYPYVA SEQ ID NO: 354 QNGVVEERSYPYVAR SEQ ID NO: 355 QIREALTQTHTAIAV SEQ ID NO: 356 YDGRTIIQHDNGYQP SEQ ID NO: 357 IPRGIEYIQQNGWE SEQ ID NO: 358 ESAYLAYRNTSLDLS SEQ ID NO: 359 RTIIQHDNGYQPNYH SEQ ID NO: 360 GYGYFQAGNNLMMIE SEQ ID NO: 361 DLRAFQHYDGRTIIQ SEQ ID NO: 362 PRGIEYIQQNGVVEE SEQ ID NO: 363 RTIIQHDNGYQPNYH SEQ ID NO: 364 TAIAVIIGIKDLRAF SEQ ID NO: 365 GYGYFQAGNNLMMIE SEQ ID NO: 366 QPNYHAVNIVGYGST SEQ ID NO: 367 QGVDYWIVRNSWDTT SEQ ID NO: 368 GRTIIQHDNGYQPNY SEQ ID NO: 369 PRGIEYIQQNGVVEE SEQ ID NO: 370 YQPNYHAVNIVGYGS SEQ ID NO: 371 GIEYIQQNGVVEERS SEQ ID NO: 372 RSLRTVTPIRMQGGC SEQ ID NO: 373 GRTIIQHDNGYQPNY SEQ ID NO: 374 QQNGVVEERSYPYVA SEQ ID NO: 375 QQNGVVEERSYPYVA SEQ ID NO: 376 TESAYLAYRNTSLDL SEQ ID NO: 377 ATESAYLAYRNTSLD SEQ ID NO: 378 TAIAVIIGIKDLRAF SEQ ID NO: 379 QPNYHAVNIVGYGST SEQ ID NO: 380 HTAIAVIIGIKDLRA SEQ ID NO: 381 DTIPRGIEYIQQNGV SEQ ID NO: 382 YDGRTIIQHDNGYQP SEQ ID NO: 383 QQNGVVEERSYPYVA SEQ ID NO: 384 LDLRSLRTVTPIRMQ SEQ ID NO: 385 CWAFSGVAATESAYL SEQ ID NO: 386 IQQNGVVEERSYPYV SEQ ID NO: 387 EYIQQNGVVEERSYP SEQ ID NO: 388 PRGIEYIQQNGVVEESEQ ID NO: 389 GYQPNYHAVNIVGYG SEQ ID NO: 390 LRSLRTVTPIRMQGG SEQ ID NO: 391 IIGIKDLRAFQHYDG SEQ ID NO: 392 RGIEYIQQNGVVEER SEQ ID NO: 393 AVIIGIKDLRAFQHY SEQ ID NO: 394 SAYLAYRNTSLDLSE SEQ ID NO: 395 PNYHAVNIVGYGSTQ SEQ ID NO: 396 GVDYWIVRNSWDTTW SEQ ID NO: 397 IPRGIEYIQQNGWE SEQ ID NO: 398 YQPNYHAVNIVGYGS SEQ ID NO: 399 IAVIIGIKDLRAFQH SEQ ID NO: 400 RAFQHYDGRTIIQHD SEQ ID NO: 401 SGYGYFQAGNNLMMI SEQ ID NO: 402 DVKQIREALTQTHTA SEQ ID NO: 403 VKQIREALTQTHTAI SEQ ID NO: 404 NVPSELDLRSLRTVT SEQ ID NO: 405 IVGYGSTQGVDYWIV SEQ ID NO: 406 GYQPNYHAVNIVGYG SEQ ID NO: 407 DGRTIIQHDNGYQPN SEQ ID NO: 408 TIIQHDNGYQPNYHA SEQ ID NO: 409 SGYGYFQAGNNLMMI SEQ ID NO: 410 TQGVDYWIVRNSWDT SEQ ID NO: 411 NIVGYGSTQGVDYWI SEQ ID NO: 412 SYPYVAREQQCRRPN SEQ ID NO: 413 GYQPNYHAVNIVGYG SEQ ID NO: 414 DSGYGYFQAGNNLMM SEQ ID NO: 415 IPRGIEYIQQNGWE SEQ ID NO: 416 LRSLRTVTPIRMQGG SEQ ID NO: 417 VNVPSELDLRSLRTV SEQ ID NO: 418 GYGYFQAGNNLMMIE SEQ ID NO: 419 PPDVKQIREALTQTH SEQ ID NO: 420 KDLRAFQHYDGRTII SEQ ID NO: 421 IQQNGVVEERSYPYV SEQ ID NO: 422 YGYFQAGNNLMMIEQ SEQ ID NO: 423 AATESAYLAYRNTSL SEQ ID NO: 424 IIGIKDLRAFQHYDG SEQ ID NO: 425 HTAIAVIIGIKDLRASEQ ID NO: 426 NGVVEERSYPYVARESEQ ID NO: 427 TAIAVIIGIKDLRAFSEQ ID NO: 428 VNIVGYGSTQGVDYWSEQ ID NO: 429 NGYQPNYHAVNIVGYSEQ ID NO: 430 RGIEYIQQNGVVEERSEQ ID NO: 431 PRGIEYIQQNGVVEESEQ ID NO: 432 VIIGIKDLRAFQHYDSEQ ID NO: 433 FSGVAATESAYLAYRSEQ ID NO: 434 RGIEYIQQNGVVEERSEQ ID NO: 435 GIKDLRAFQHYDGRTSEQ ID NO: 436 DLRSLRTVTPIRMQGSEQ ID NO: 437 NGVVEERSYPYVARESEQ ID NO: 438 YPYVAREQQCRRPNSSEQ ID NO: 439 IKDLRAFQHYDGRTISEQ ID NO: 440 RAFQHYDGRTIIQHDSEQ ID NO: 441 YDGRTIIQHDNGYQPSEQ ID NO: 442 IAVIIGIKDLRAFQHSEQ ID NO: 443 KQIREALTQTHTAIASEQ ID NO: 444 IAVIIGIKDLRAFQHSEQ ID NO: 445 TIPRGIEYIQQNGVVSEQ ID NO: 446 DSGYGYFQAGNNLMMSEQ ID NO: 447 RSYPYVAREQQCRRPSEQ ID NO: 448 PNYHAVNIVGYGSTQv) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 2 house dust mite polypeptide (e.g., as depicted in Example 1 (e.g., as depicted in Figure 1) and / or 2 and / or Example 2 and / or Example 3 and / or Example 4 herein, e.g., as in Table 2 and / or 3 herein) (e.g., Der p 2 Isoform 0110), preferably selected from the group consisting of: (a’”), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a’”) SEQ ID NO: 449(DQVDVKDCANHEIKKVLVPGCHGSEPCIIHRGKPFQLEAVFEAN QNSKTAKI El KASI DGLEVDVPGI DPNACHYM KCPLVKGQQYDI K YTWNVPKIAPKSENVVVTVKVMGDNGVLACAIATHAKIRD); vi) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 2-derived HLA-binding peptides (e.g., as depicted in in Example 1 (e.g., as depicted in Figure 1) and / or 2 and / or Example 3 and / or Example 4 herein, e.g., as in Table 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 450 LEAVFEANQNSKTAKSEQ ID NO: 451 EAVFEANQNSKTAKISEQ ID NO: 452 QLEAVFEANQNSKTASEQ ID NO: 453 DIKYTWNVPKIAPKSSEQ ID NO: 454 YDIKYTWNVPKIAPKSEQ ID NO: 455 AVFEANQNSKTAKIESEQ ID NO: 456 QYDIKYTWNVPKIAPSEQ ID NO: 457 IKYTWNVPKIAPKSESEQ ID NO: 458 KASI DGLEVDVPGI DSEQ ID NO: 459 FQLEAVFEANQNSKTSEQ ID NO: 460 QYDIKYTWNVPKIAPSEQ ID NO: 461 VFEANQNSKTAKIEISEQ ID NO: 462 IKASIDGLEVDVPGISEQ ID NO: 463 IDGLEVDVPGIDPNASEQ ID NO: 464 KYTWNVPKIAPKSENSEQ ID NO: 465 QQYDIKYTWNVPKIASEQ ID NO: 466 SIDGLEVDVPGIDPNSEQ ID NO: 467 QQYDIKYTWNVPKIASEQ ID NO: 468 YDIKYTWNVPKIAPKSEQ ID NO: 469 IDGLEVDVPGIDPNASEQ ID NO: 470 GKPFQLEAVFEANQNSEQ ID NO: 471 EIKASIDGLEVDVPGSEQ ID NO: 472 GKPFQLEAVFEANQNSEQ ID NO: 473 VVVTVKVMGDNGVLASEQ ID NO: 474 ASIDGLEVDVPGIDPSEQ ID NO: 475 DGLEVDVPGIDPNAC SEQ ID NO: 476 SIDGLEVDVPGIDPN SEQ ID NO: 477 GQQYDIKYTWNVPKI SEQ ID NO: 478 GKPFQLEAVFEANQN SEQ ID NO: 479 DIKYTWNVPKIAPKS SEQ ID NO: 480 LEAVFEANQNSKTAK SEQ ID NO: 481 RGKPFQLEAVFEANQ SEQ ID NO: 482 EAVFEANQNSKTAKI SEQ ID NO: 483 PKSENVVVTVKVMGD SEQ ID NO: 484 ASIDGLEVDVPGIDP SEQ ID NO: 485 VPKIAPKSENVVVTV SEQ ID NO: 486 LEAVFEANQNSKTAK SEQ ID NO: 487 DGLEVDVPGIDPNAC SEQ ID NO: 488 VTVKVMGDNGVLACA SEQ ID NO: 489 TAKIEIKASIDGLEV SEQ ID NO: 490 VTVKVMGDNGVLACA SEQ ID NO: 491 TVKVMGDNGVLACAI SEQ ID NO: 492 TVKVMGDNGVLACAI SEQ ID NO: 493 NVPKIAPKSENVVVT SEQ ID NO: 494 RGKPFQLEAVFEANQ SEQ ID NO: 495 RGKPFQLEAVFEANQ SEQ ID NO: 496 EAVFEANQNSKTAKI SEQ ID NO: 497 GKPFQLEAVFEANQN SEQ ID NO: 498 QYDIKYTWNVPKIAP SEQ ID NO: 499 ASIDGLEVDVPGIDP SEQ ID NO: 500 SENVVVTVKVMGDNG SEQ ID NO: 501 KTAKIEIKASIDGLE SEQ ID NO: 502 VPGIDPNACHYMKCP SEQ ID NO: 503 APKSENVVVTVKVMG SEQ ID NO: 504 DIKYTWNVPKIAPKS SEQ ID NO: 505 VVTVKVMGDNGVLAC SEQ ID NO: 506 QLEAVFEANQNSKTA SEQ ID NO: 507 GQQYDIKYTWNVPKI SEQ ID NO: 508 YDIKYTWNVPKIAPK SEQ ID NO: 509 KGQQYDIKYTWNVPK SEQ ID NO: 510 QYDIKYTWNVPKIAP SEQ ID NO: 511 DIKYTWNVPKIAPKSSEQ ID NO: 512 VDVPGIDPNACHYMKSEQ ID NO: 513 KSENVVVTVKVMGDNSEQ ID NO: 514 RGKPFQLEAVFEANQSEQ ID NO: 515 KGQQYDIKYTWNVPKSEQ ID NO: 516 VVTVKVMGDNGVLACSEQ ID NO: 517 YDIKYTWNVPKIAPKSEQ ID NO: 518 NVVVTVKVMGDNGVLSEQ ID NO: 519 VVVTVKVMGDNGVLASEQ ID NO: 520 IDGLEVDVPGIDPNASEQ ID NO: 521 QQYDIKYTWNVPKIASEQ ID NO: 522 IKYTWNVPKIAPKSESEQ ID NO: 523 VVTVKVMGDNGVLACSEQ ID NO: 524 WNVPKIAPKSENVVVSEQ ID NO: 525 KASIDGLEVDVPGIDSEQ ID NO: 526 GKPFQLEAVFEANQNSEQ ID NO: 527 IAPKSENVVVTVKVMSEQ ID NO: 528 KSENVVVTVKVMGDNSEQ ID NO: 529 KPFQLEAVFEANQNSSEQ ID NO: 530 SENVVVTVKVMGDNGSEQ ID NO: 531 PKIAPKSENVVVTVKSEQ ID NO: 532 GQQYDIKYTWNVPKISEQ ID NO: 533 QQYDIKYTWNVPKIASEQ ID NO: 534 DVPGIDPNACHYMKCSEQ ID NO: 724 DQVDVKDCANHEIKKSEQ ID NO: 725 HGSEPCIIHRGKSEQ ID NO: 726 HGSEPCIIHRGKSEQ ID NO: 727 HGSEPCIIHRGKPFQSEQ ID NO: 728 HGSEPCIIHRGKPFQLEASEQ ID NO: 729 EPCIIHRGKPFQLEASEQ ID NO: 730 EPCIIHRGKPFQLEALFESEQ ID NO: 731 LEALFEANQNTKNAKSEQ ID NO: 732 LEALFEANQNTKNAKSEQ ID NO: 733 LEALFEANQNTKNAKSEQ ID NO: 734 LEALFEANQNTKNAKIEIKASIDG (+49-60Epitop corresponding to SEQ ID NO: 748 (NAKIEIKASIDG )SEQ ID NO: 735 LFEANQNTKNAKSEQ ID NO: 736 NTKNAKIEIKASSEQ ID NO: 737 DVPGIDPNACHYVKCPLVKGQSEQ ID NO: 738 GIDPNACHYVKCPLVSEQ ID NO: 739 PNACHYVKCPLVKGQSEQ ID NO: 740 QYDIKYTWNVPKIAPSEQ ID NO: 741 VPKIAPKSENVVSEQ ID NO: 742 VPKIAPKSENVVVTVKVLSEQ ID NO: 743 GVLACAIATHAKvii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 2 house dust mite polypeptide (e.g., Der f 2 Isoform 0102), preferably selected from the group consisting of: (a””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a””) SEQ ID NO: 535 (DQVDVKDCANNEIKKVMVDGCHGSDPCIIHRGKPFTLEALFDAN QNTKTAKIEIKASLDGLEIDVPGIDTNACHFMKCPLVKGQQYDIKY TWNVPKIAPKSENVWTVKLIGDNGVLACAIATHGKIRD); viii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 2-derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 536 LEALFDANQNTKTAKSEQ ID NO: 537 EALFDANQNTKTAKISEQ ID NO: 538 DIKYTWNVPKIAPKSSEQ ID NO: 539 YDIKYTWNVPKIAPKSEQ ID NO: 540 TLEALFDANQNTKTASEQ ID NO: 541 QYDIKYTWNVPKIAPSEQ ID NO: 542 ALFDANQNTKTAKIESEQ ID NO: 543 IKYTWNVPKIAPKSESEQ ID NO: 544 NNEIKKVMVDGCHGS SEQ ID NO: 545 ANNEIKKVMVDGCHG SEQ ID NO: 546 QYDIKYTWNVPKIAP SEQ ID NO: 547 KASLDGLEIDVPGID SEQ ID NO: 548 KYTWNVPKIAPKSEN SEQ ID NO: 549 QQYDIKYTWNVPKIA SEQ ID NO: 550 QQYDIKYTWNVPKIA SEQ ID NO: 551 CANNEIKKVMVDGCH SEQ ID NO: 552 VTVKLIGDNGVLACA SEQ ID NO: 553 LDGLEIDVPGIDTNA SEQ ID NO: 554 NEIKKVMVDGCHGSD SEQ ID NO: 555 YDIKYTWNVPKIAPK SEQ ID NO: 556 FTLEALFDANQNTKT SEQ ID NO: 557 TVKLIGDNGVLACAI SEQ ID NO: 558 SLDGLEIDVPGIDTN SEQ ID NO: 559 LDGLEIDVPGIDTNA SEQ ID NO: 560 TVKLIGDNGVLACAI SEQ ID NO: 561 VTVKLIGDNGVLACA SEQ ID NO: 562 IKASLDGLEIDVPGI SEQ ID NO: 563 LFDANQNTKTAKIEI SEQ ID NO: 564 VVTVKLIGDNGVLAC SEQ ID NO: 565 GQQYDIKYTWNVPKI SEQ ID NO: 566 DGLEIDVPGIDTNAC SEQ ID NO: 567 SLDGLEIDVPGIDTN SEQ ID NO: 568 DIKYTWNVPKIAPKS SEQ ID NO: 569 VVVTVKLIGDNGVLA SEQ ID NO: 570 ASLDGLEIDVPGIDT SEQ ID NO: 571 VPKIAPKSENVVVTV SEQ ID NO: 572 PKSENVVVTVKLIGD SEQ ID NO: 573 NVPKIAPKSENVVVT SEQ ID NO: 574 DGLEIDVPGIDTNAC SEQ ID NO: 575 TVKLIGDNGVLACAI SEQ ID NO: 576 VVTVKLIGDNGVLAC SEQ ID NO: 577 VVVTVKLIGDNGVLA SEQ ID NO: 578 EIKASLDGLEIDVPG SEQ ID NO: 579 EIKKVMVDGCHGSDP SEQ ID NO: 580 SENVVVTVKLIGDNGSEQ ID NO: 581 QYDIKYTWNVPKIAP SEQ ID NO: 582 GKPFTLEALFDANQN SEQ ID NO: 583 VTVKLIGDNGVLACA SEQ ID NO: 584 VKLIGDNGVLACAIA SEQ ID NO: 585 TAKIEIKASLDGLEI SEQ ID NO: 586 KSENVVVTVKLIGDN SEQ ID NO: 587 DIKYTWNVPKIAPKS SEQ ID NO: 588 KTAKIEIKASLDGLE SEQ ID NO: 589 VKLIGDNGVLACAIA SEQ ID NO: 590 GQQYDIKYTWNVPKI SEQ ID NO: 591 YDIKYTWNVPKIAPK SEQ ID NO: 592 KGQQYDIKYTWNVPK SEQ ID NO: 593 QYDIKYTWNVPKIAP SEQ ID NO: 594 DIKYTWNVPKIAPKS SEQ ID NO: 595 ASLDGLEIDVPGIDT SEQ ID NO: 596 LEALFDANQNTKTAK SEQ ID NO: 597 EALFDANQNTKTAKI SEQ ID NO: 598 SENVVVTVKLIGDNG SEQ ID NO: 599 APKSENVVVTVKLIG SEQ ID NO: 600 KGQQYDIKYTWNVPK SEQ ID NO: 601 EIKKVMVDGCHGSDP SEQ ID NO: 602 YDIKYTWNVPKIAPK SEQ ID NO: 603 QQYDIKYTWNVPKIA SEQ ID NO: 604 RGKPFTLEALFDANQ SEQ ID NO: 605 IKYTWNVPKIAPKSE SEQ ID NO: 606 WNVPKIAPKSENVVV SEQ ID NO: 607 ASLDGLEIDVPGIDT SEQ ID NO: 608 LEALFDANQNTKTAK SEQ ID NO: 609 VVVTVKLIGDNGVLA SEQ ID NO: 610 KSENVVVTVKLIGDN SEQ ID NO: 611 IKKVMVDGCHGSDPC SEQ ID NO: 612 PKIAPKSENVVVTVK SEQ ID NO: 613 KASLDGLEIDVPGID SEQ ID NO: 614 VKLIGDNGVLACAIA SEQ ID NO: 615 ENVVVTVKLIGDNGV SEQ ID NO: 616 GQQYDIKYTWNVPKI SEQ ID NO: 617 QQYDIKYTWNVPKIASEQ ID NO: 618 ENVVVTVKLIGDNGVSEQ ID NO: 619 NEIKKVMVDGCHGSDSEQ ID NO: 620 PKSENVVVTVKLIGDix) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 23 house dust mite polypeptide (e.g., Der p 23 Isoform 0101), preferably selected from the group consisting of: (a’””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a’””) SEQ ID NO: 621 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT);x)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 622 SRFGYFADPKDPHKFSEQ ID NO: 623 RFGYFADPKDPHKFYSEQ ID NO: 624 PSRFGYFADPKDPHKSEQ ID NO: 625 RFGYFADPKDPHKFYSEQ ID NO: 626 SRFGYFADPKDPHKFSEQ ID NO: 627 PSRFGYFADPKDPHKSEQ ID NO: 628 PHKFYICSNWEAVHKSEQ ID NO: 629 FGYFADPKDPHKFYISEQ ID NO: 630 FGYFADPKDPHKFYISEQ ID NO: 631 PHKFYICSNWEAVHKSEQ ID NO: 632 CPSRFGYFADPKDPHSEQ ID NO: 633 RFGYFADPKDPHKFYSEQ ID NO: 634 PSRFGYFADPKDPHKSEQ ID NO: 635 SRFGYFADPKDPHKFSEQ ID NO: 636 DPHKFYICSNWEAVHSEQ ID NO: 637 CPSRFGYFADPKDPHSEQ ID NO: 638 DPHKFYICSNWEAVHSEQ ID NO: 639 PSRFGYFADPKDPHKSEQ ID NO: 640 HKFYICSNWEAVHKDSEQ ID NO: 641 PSRFGYFADPKDPHKSEQ ID NO: 642 PSRFGYFADPKDPHKSEQ ID NO: 643 GYFADPKDPHKFYICSEQ ID NO: 644 GYFADPKDPHKFYICSEQ ID NO: 645 PHKFYICSNWEAVHKSEQ ID NO: 646 PHKFYICSNWEAVHKSEQ ID NO: 647 I I I VHPTTTEQPDDKxi) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 23 house dust mite polypeptide (e.g., Der f 23 Isoform 0201) sequence identity to Der f 23 house dust mite polypeptide selected from the group consisting of: (a”””), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a”””) SEQ ID NO: 648 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT); andSEQ ID NO: 744 (DIDHDDDPTTMIDVQTTTVQPSDEFECPTR FGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT); xii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 649 TTMIDVQ I I I VQPSDSEQ ID NO: 650 PTTMIDVQ I I I VORSSEQ ID NO: 651 TMIDVQI I I VQPSDESEQ ID NO: 652 DPTTMIDVQ I I I VQPSEQ ID NO: 653 RFGYFADPKDPCKFYSEQ ID NO: 654 TRFGYFADPKDPCKFSEQ ID NO: 655 PTRFGYFADPKDPCKSEQ ID NO: 656 MIDVQ I I I VQPSDEFSEQ ID NO: 657 RFGYFADPKDPCKFYSEQ ID NO: 658 TRFGYFADPKDPCKFSEQ ID NO: 659 FGYFADPKDPCKFYISEQ ID NO: 660 PTRFGYFADPKDPCKSEQ ID NO: 661 PTTMIDVQ I I I VORSSEQ ID NO: 662 RFGYFADPKDPCKFYSEQ ID NO: 663 DPTTMIDVQ I I I VQPSEQ ID NO: 664 CPTRFGYFADPKDPCSEQ ID NO: 665 TRFGYFADPKDPCKFSEQ ID NO: 666 PTRFGYFADPKDPCKSEQ ID NO: 667 IDVQTTTVQPSDEFESEQ ID NO: 668 FGYFADPKDPCKFYISEQ ID NO: 669 TMIDVQI I I VQPSDESEQ ID NO: 670 DDPTTMIDVQI I I VQSEQ ID NO: 671 PCKFYICSNWEAIHKSEQ ID NO: 672 MIDVQ I I I VQPSDEFc) optionally, a nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673 (GGGGS);d) a nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) transmembrane domains (e.g., derived from LAMP-1 (e.g., having Uniprot accession numbers: P11438 or P11279), LAMP-2 (e.g., having Uniprot accession number: P13473), HLA class II histocompatibility antigen gamma chain (e.g., having Uniprot accession number: P04233), HLA class I histocompatibility antigen, A alpha chain (e.g., having Uniprot accession number: P04439), HLA class I histocompatibility antigen, B alpha chain (e.g., having Uniprot accession number: P01889), HLA class I histocompatibility antigen, C alpha chain (e.g., having Uniprot accession number: P10321) and / or Transferrin receptor protein 1 (e.g., having Uniprot accession number: P02786) and one or more cytosolic domains (e.g., derived from LAMP-1 (e.g., having Uniprot accession numbers: P11438 or P11279), LAMP-2 (e.g., having Uniprot accession number: P13473), HLA class II histocompatibility antigen gamma chain (e.g., having Uniprot accession number: P04233), HLA class Ihistocompatibility antigen, A alpha chain (e.g., having Uniprot accession number: P04439), HLA class I histocompatibility antigen, B alpha chain (e.g., having Uniprot accession number: P01889), HLA class I histocompatibility antigen, C alpha chain (e.g., having Uniprot accession number: P10321) and / or Transferrin receptor protein 1 (e.g., having Uniprot accession number: P02786); preferably said one or more transmembrane domains and one or more cytosolic domains comprising or consisting of the human SEQ ID NO: 674 (MLIPIAVGGALAGLVLIVLIAYLVGRKRSHAGYQTI) and / or murine SEQ ID NO: 675 (MLIPIAVGGALAGLVLIVLIAYLIGRKRSHAGYQTI).A nucleic acid construct, preferably a RNA construct, comprising or consisting of the following sequences (a), (b), (d) and optionally (c), wherein said sequences are in-frame, preferably in the following order, wherein:(a) a nucleic acid sequence encoding for a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1 , further preferably the polypeptide fragment is at least 15 amino acids long, even further preferably the signal polypeptide has at least 75% sequence identity to SEQ ID NO:1 or SEQ ID NO: 2, most preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 or the murine SEQ ID NO: 2;(b) a nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides, preferably allergens, selected from the group consisting of (i)-(vii) :i) a polypeptide comprising or consisting of one or more Derp 1-derived HLA- binding peptides, wherein said one or more Der p 1-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 6-283; 682-723; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 4, and SEQ ID NO: 3;ii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite-derived polypeptide of SEQ ID NO: 285, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01;iii) a polypeptide comprising or consisting of one or more Der f 1-derived HLA- binding peptides, wherein said one or more Der f 1-derived HLA-bindingpeptides are selected from the group consisting of: SEQ ID NOs: 287-448; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 1 dust mite polypeptide selected from the group consisting of SEQ ID NO: 284 and SEQ ID NO: 286;iv) a polypeptide comprising or consisting of one or more Der p 2-derived HLA- binding peptides, wherein said one or more Der p 2-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 450-534; 724-743; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449;v) a polypeptide comprising or consisting of one or more Der f 2-derived HLA- binding peptides, wherein said one or more Der f 2-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 536-620; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide of SEQ ID NO: 535;vi) a polypeptide comprising or consisting of one or more Der p 23-derived HLA-binding peptides, wherein said one or more Der p 23-derived HLA- binding peptides are selected from the group consisting of: SEQ ID NOs: 622-647; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1 *03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621;vii) a polypeptide comprising or consisting of one or more Der f 23-derived HLA-binding peptides, wherein said one or more Der f 23-derived HLA- binding peptides selected from the group consisting of: SEQ ID NOs: 649- 672; preferably said polypeptide has an antigenic specificity presented inthe context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NOs: 648 or 744 ;viii) any combination of the above i-vii;(c) optionally, a nucleic acid sequence encoding for one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673; (d) a nucleic acid sequence encoding for, preferably in the following order:d’) one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; andd”) one or more cytosolic domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1;preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) have a sequence identity of at least 75% to SEQ ID NO: 674 or murine SEQ ID NO: 675; further preferably, said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) comprising or consisting of the human SEQ ID NO: 674 or murine SEQ ID NO: 675.The nucleic acid construct of any one of the preceding items, wherein said construct encoding for enzymatically-inactive or enzymatically-active polypeptide / s.The nucleic acid construct of any one of the preceding items, wherein said house dust mite polypeptides (e.g., allergens) comprising a propeptide, preferably in case of the Der p 1 and / or Der f 1 ; which optionally are used for the correct folding of the corresponding polypeptide.The nucleic acid construct of any one of the preceding items, wherein said construct is a recombinant construct.The nucleic acid construct of any one of the preceding items, wherein said construct is further optimized, preferably optimized for mammalian (e.g., human) expression, further preferably said construct is optimized by one or more means selected from the group consisting of:a) codon-optimization, e.g., altering codons encoding for amino acids to enhance translation efficiency in human cells and / or minimize content that could lead to rapid degradation or unwanted immune responses;b) removing of the slippery site / s, e.g., removing sequences where ribosomal frameshifting can occur during the translation process;c) reducing the uridine (II) content of the RNA construct;d) incorporating modified nucleosides like pseudouridine (^P) instead of uridine, e.g., to evade immune detection and / or reduce inflammation;e) modifying the UTRs, e.g., to enhance mRNA stability and / or translational efficiency; f) adding a cap structure at the 5' end of the mRNA to increase stability and / or mimic endogenous mRNA (e.g., for improving translation);g) modifying the length of the poly(A) tail, e.g., to balance between mRNA stability and / or translational efficiency;h) minimizing secondary structures that can impede the translation process and / or lead to premature degradation;i) modifying GC content, e.g., to avoid extreme thermostability and / or instability of the mRNA strand, which can affect both translation and / or stability; andj) removing double-stranded RNA contaminants that can trigger immune responses. The nucleic acid construct of any one of the preceding items, wherein said construct is a single stranded RNA and / or is essentially free (e.g., free) from double-stranded RNA, e.g., to decrease the risk of innate immune activation.The nucleic acid construct of any one of the preceding items, wherein said construct is encapsulated in lipid nanoparticles (LNPs) or polymersomes, preferably to protect the mRNA from degradation and / or facilitate cellular uptake.The nucleic acid construct of any one of the preceding items, wherein said construct is an expression vector (e.g., a viral expression vector or mRNA expression vector).The nucleic acid construct of any one of the preceding items, wherein said construct encoding for a polypeptide comprising or consisting of a polypeptide selected from the group consisting of:SEQ ID NO: 676 MAAPGARRPLLLLLLAGLAHGASARPSSIKTFEEYKKAFNKSY ATFEDEEAARKNFLESVKYVQSNGGAINHLSDLSLDEFKNRFL MSAEAFEHLKTQFDLNAETNACSINGNAPAEIDLRQMRTVTPI RMQGGCGSCWAFSGVAATESAYLAYRNQSLDLAEQELVDCA SQHGCHGDTIPRGIEYIQHNGWQESYYRYVAREQSCRRPNA QRFGISNYCQIYPPNVNKIREALAQTHSAIAVIIGIKDLDAFRHY DGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYWIVRNSWDTN WGDNGYGYFAAN I DLM M I EEYPYVVI LGGGGSM LI PIAVGGAL AGLVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 677 MAAPGARRPLLLLLLAGLAHGASARPASIKTFEEFKKAFNKNY ATVEEEEVARKNFLESLKYVEANKGAINHLSDLSLDEFKNRYL MSAEAFEQLKTQFDLNAETSACRINSVNVPSELDLRSLRTVTP IRMQGGCGSCWAFSGVAATESAYLAYRNTSLDLSEQELVDCA SQHGCHGDTIPRGIEYIQQNGVVEERSYPYVAREQQCRRPNS QHYGISNYCQIYPPDVKQIREALTQTHTAIAVIIGIKDLRAFQHY DGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDYWIVRNSWDTT WGDSGYGYFQAG N N LM M I EQYPYVVI MGGGGSM LI PI AVGG ALAGLVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 678 MAAPGARRPLLLLLLAGLAHGASADQVDVKDCANHEIKKVLV PGCHGSEPCIIHRGKPFQLEAVFEANQNSKTAKIEIKASIDGLE VDVPGI DPNACHYM KCPLVKGQQYDI KYTWN VPKIAPKSEN V VVTVKVMGDNGVLACAIATHAKIRDGGGGSMLIPIAVGGALAG LVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 679 MAAPGARRPLLLLLLAGLAHGASADQVDVKDCANNEIKKVMV DGCHGSDPCIIHRGKPFTLEALFDANQNTKTAKIEIKASLDGLE I DVPGI DTNACH FM KCPLVKGQQYDI KYTWN VPKIAPKSEN VV VTVKLIGDNGVLACAIATHGKIRDGGGGSMLIPIAVGGALAGLV LIVLIAYLIGRKRSHAGYQTISEQ ID NO: 680 MAAPGARRPLLLLLLAGLAHGASAANDNDDDP I I I VHP LTTE QPDDKFECPSRFGYFADPKDPHKFYICSNWEAVHKDCPGNT RWNEDEETCTGGGGSMLIPIAVGGALAGLVLIVLIAYLIGRKRS HAGYQTISEQ ID NO: 681 MAAPGARRPLLLLLLAGLAHGASADIDHDDDPTTMIDVQ I I I V QPSDEFECPTRFGYFADPKDPCKFYICSNWEAIHKSCPGNTR WNEKELTCTGGGGSMLIPIAVGGALAGLVLIVLIAYLIGRKRSH AGYQTIor said construct encoding for a polypeptide comprising or consisting of polypeptide / s selected from the group consisting of: SEQ ID NOs: 749, 751, 753, 755, 757 and 759 (e.g., as shown in Examples 3-4 herein).The nucleic acid construct of any one of the preceding items, wherein said nucleic acid is a RNA molecule, preferably an mRNA molecule.The nucleic acid construct of any one of the preceding items, wherein the nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more, preferably 3 or 6, e.g., as depicted in Example 1 and / or Example 2, Example 3 and / or Example 4 herein, e.g., Table 2 and / or 3) house dust mite polypeptides (e.g., Isoallergen and variants), preferably selected from the group consisting of or comprising one or more of the following polypeptides:Isoallergen and GenBank GenBank Protein UniProt variants NucleotideAAB60215Der p 1.0101 U11695 (variant) P08176 (variant)(variant)Der p 1.0102 U11695 AAB60215 P08176AAB60215Der p 1.0103 U 11695 (variant) P08176 (variant)(variant)Der p 1.0104 U11695 (variant) P08176 (variant)Der p 1.0105 U 11695 (variant) P08176 (variant)Der p 1.0106 U11695 (variant) P08176 (variant)Der p 1.0107 U 11695 (variant) P08176 (variant)Der p 1.0108 U 11695 (variant) P08176 (variant)Der p 1.0109 U11695 (variant) P08176 (variant)Der p 1.0110 U 11695 (variant) P08176 (variant)Isoallergen and GenBank GenBank Protein UniProt variants NucleotideDer p 1.0111 U11695 (variant) P08176 (variant)Der p 1.0112 U 11695 (variant) P08176 (variant)DQ185508Der p 1.0113 ABA39435 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0114 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0115 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0116 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0117 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0118 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0119 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0120 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0121 Q3HWZ5 (variant)(variant)Isoallergen and GenBank GenBank Protein UniProt variants NucleotideDQ185508Der p 1.0122 Q3HWZ5 (variant)(variant)DQ185508Der p 1.0123 Q3HWZ5 (variant)(variant)Der p 1.0124 FM 177224 CAQ68250 C7T6L6Derf 1.0101 AB034946 BAC53948 Q58A71DQ185509Der f 1.0102 Q3HWZ4 (variant)(variant)DQ185509Derf 1.0103 Q3HWZ4 (variant)(variant)DQ185509Derf 1.0104 Q3HWZ4 (variant)(variant)DQ185509Derf 1.0105 Q3HWZ4 (variant)(variant)AB034946Derf 1.0106 BAC53948 P16311(variant)Derf 1.0108 EF139428 ABL84749 A1YW11Derf 1.0109 EF139429 ABL84750 A1YW12Derf 1.0110 EF139430 ABL84751 A1YW13Isoallergen and GenBank GenBank Protein UniProt variants NucleotideDer p 2.0101 AF276239 AAF86462 P49278Der p 2.0102 P49278 (variant)Der p 2.0103 P49278 (variant)Der p 2.0104 P49278 (variant)Der p 2.0105 P49278 (variant)Der p 2.0106 P49278 (variant)Der p 2.0107 P49278 (variant)Der p 2.0108 P49278 (variant)Der p 2.0109Der p 2.0110 FM 177223 CAQ68249 C7T6L5Der p 2.0111Der p 2.0112Der p 2.0113Der p 2.0114 AM263560 CAK22338 Q1H8P8Isoallergen and GenBank GenBank Protein UniProt variants NucleotideDer p 2.0115 FM 177223 CAQ68249 C7T6L5Derf 2.0101 D 10447 BAA01239 Q00855 (variant)Der f 2.0102 D 10448 BAA01240 Q00855Der f 2.0103 D 10449 BAA01241 Q00855 (variant)Der f 2.0104Der f 2.0105 AY066008 AAL47677 Q8WQK5Der f 2.0106 AJ862836 CAI05848 Q5TIW2Der f 2.0107 AJ862837 CAI05849 Q5TIW1Der f 2.0108 AJ862838 CAI05850 Q5TIW0Der f 2.0109 DQ185511 ABA39438 Q3HWZ2Derf 2.0110Der f 2.0111Derf 2.0112 AY283288 AAP35073 A1KXH0Derf 2.0113Isoallergen and GenBank GenBank Protein UniProt variants NucleotideDerf 2.0114Derf 2.0115Derf 2.0116 EF205129 A3F5F1Derf 2.0117Der p 23.0101 EU414751.1 ACB46292 L7N6F8Derf 23.0101 KU 166910 ALU66112 A0A0U3JM87Der f 23.0201 KM009999 AIO08855 A0A088SAW7The nucleic acid construct of any one of the preceding items, wherein said nucleic acid is a monocistronic or polycistronic mRNA molecule.The nucleic acid construct of any one of the preceding items, wherein said nucleic acid is capable of not triggerring a B-cell response, preferably via competition of the IgGs with the IgEs.The nucleic acid construct of any one of the preceding items, wherein said nucleic acid comprises one or more modified nucleosides, preferably said one or more modified nucleosides are one or more pseudouridine residues comprising:a) m1lP (1-methylpseudouridine);b) m1acp3lP (1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine);c) ^Pm (2'-0-methylpseudouridine);d) m5D (5-methyldihydrouridine);e) m3^ (3-methylpseudouridine); orf) any combination thereof.The nucleic acid construct of any one of the preceding items, further comprising one or more of the following:a) a poly-A tail;b) an m7GpppG cap;c) a cap-independent translational enhancer; andd) 5' and / or 3' untranslated regions that enhance translation.The nucleic acid construct of any one of the preceding items, wherein said nucleic acid is an endo-lysosomal-targeted mRNA.A polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the following polypeptide sequences, preferably in the following order:a) a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1, further preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 (MAAPGSARRPLLLLLLLLLLGLMHCASA) and / or the murine SEQ ID NO: 2 (MAAPGARRPLLLLLLAGLAHGASA);b) one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides (e.g., as depicted in Examples 1 and / or 2 herein, e.g., in Table 2 and / or 3, preferably selected from the group consisting of:i) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Der p 1 house dust mite polypeptide (e.g., Der p 1 Isoform 0102), preferably selected from the group consisting of: (a’)-(c’), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA- DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA- DRB5*01:01:a’) SEQ ID NO: 3 (TNACSINGNAPAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAAT ESAYLAYRNQSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNG VVQESYYRYVAREQSCRRPNAQRFGISNYCQIYPPNVNKIREAL AQTHSAIAVIIGIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGY SNAQGVDYWIVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYW IL);b’) SEQ ID NO: 4 (RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAE); and c) SEQ ID NO: 5 (RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAETNACSINGN APAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAATESAYLAYRN QSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNGVVQESYYRYVAREQSCRRPNAQRFGISNYCQIYPPNVNKIREALAQTHSAIAVII GIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYW IVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYVVIL); ii) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 1-derived HLA-binding peptides (e.g., as depicted in Table 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA- DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NO: 6 HAVNIVGYSNAQGVDSEQ ID NO: 7 AVNIVGYSNAQGVDYSEQ ID NO: 8 YHAVNIVGYSNAQGVSEQ ID NO: 9 VNIVGYSNAQGVDYWSEQ ID NO: 10 ESVKYVQSNGGAINHSEQ ID NO: 11 SVKYVQSNGGAINHLSEQ ID NO: 12 LESVKYVQSNGGAINSEQ ID NO: 13 SYATFEDEEAARKNFSEQ ID NO: 14 YATFEDEEAARKNFLSEQ ID NO: 15 YLAYRNQSLDLAEQESEQ ID NO: 16 AYLAYRNQSLDLAEQSEQ ID NO: 17 LAYRNQSLDLAEQELSEQ ID NO: 18 FSGVAATESAYLAYRSEQ ID NO: 19 KSYATFEDEEAARKNSEQ ID NO: 20 DNGYQPNYHAVNIVGSEQ ID NO: 21 DLSLDEFKNRFLMSASEQ ID NO: 22 RDNGYQPNYHAVNIVSEQ ID NO: 23 ESAYLAYRNQSLDLASEQ ID NO: 24 SAYLAYRNQSLDLAESEQ ID NO: 25 AFSGVAATESAYLAYSEQ ID NO: 26 ATFEDEEAARKNFLESEQ ID NO: 27 TESAYLAYRNQSLDLSEQ ID NO: 28 SVKYVQSNGGAINHLSEQ ID NO: 29 IREALAQTHSAIAVISEQ ID NO: 30 VKYVQSNGGAINHLSSEQ ID NO: 31 VKYVQSNGGAINHLSSEQ ID NO: 32 ESVKYVQSNGGAINHSEQ ID NO: 33 ATESAYLAYRNQSLD SEQ ID NO: 34 QRDNGYQPNYHAVNI SEQ ID NO: 35 SDLSLDEFKNRFLMS SEQ ID NO: 36 LDAFRHYDGRTIIQR SEQ ID NO: 37 PRGIEYIQHNGVVQE SEQ ID NO: 38 NIVGYSNAQGVDYWI SEQ ID NO: 39 KIREALAQTHSAIAV SEQ ID NO: 40 NYHAVNIVGYSNAQG SEQ ID NO: 41 WAFSGVAATESAYLA SEQ ID NO: 42 REALAQTHSAIAVII SEQ ID NO: 43 SGVAATESAYLAYRN SEQ ID NO: 44 FLESVKYVQSNGGAI SEQ ID NO: 45 FEHLKTQFDLNAETN SEQ ID NO: 46 NGYQPNYHAVNIVGY SEQ ID NO: 47 DLDAFRHYDGRTIIQ SEQ ID NO: 48 PSSIKTFEEYKKAFN SEQ ID NO: 49 IPRGIEYIQHNGWQ SEQ ID NO: 50 DAFRHYDGRTIIQRD SEQ ID NO: 51 AVNIVGYSNAQGVDY SEQ ID NO: 52 ACSINGNAPAEIDLR SEQ ID NO: 53 LESVKYVQSNGGAIN SEQ ID NO: 54 SAYLAYRNQSLDLAE SEQ ID NO: 55 PRGIEYIQHNGVVQE SEQ ID NO: 56 YGYFAANIDLMMIEE SEQ ID NO: 57 RPSSIKTFEEYKKAF SEQ ID NO: 58 KKAFNKSYATFEDEE SEQ ID NO: 59 QPNYHAVNIVGYSNA SEQ ID NO: 60 NAPAEIDLRQMRTVT SEQ ID NO: 61 KTQFDLNAETNACSI SEQ ID NO: 62 AYRNQSLDLAEQELV SEQ ID NO: 63 LKTQFDLNAETNACS SEQ ID NO: 64 GNAPAEIDLRQMRTV SEQ ID NO: 65 PRGIEYIQHNGVVQE SEQ ID NO: 66 VNIVGYSNAQGVDYW SEQ ID NO: 67 YQPNYHAVNIVGYSN SEQ ID NO: 68 GGAINHLSDLSLDEF SEQ ID NO: 69 HAVNIVGYSNAQGVDSEQ ID NO: 70 LESVKYVQSNGGAIN SEQ ID NO: 71 NGGAINHLSDLSLDE SEQ ID NO: 72 LSDLSLDEFKNRFLM SEQ ID NO: 73 GYGYFAANIDLMMIE SEQ ID NO: 74 KYVQSNGGAINHLSD SEQ ID NO: 75 AFEHLKTQFDLNAET SEQ ID NO: 76 NKSYATFEDEEAARK SEQ ID NO: 77 GIEYIQHNGWQESY SEQ ID NO: 78 QPNYHAVNIVGYSNA SEQ ID NO: 79 LSLDEFKNRFLMSAE SEQ ID NO: 80 NKSYATFEDEEAARK SEQ ID NO: 81 KDLDAFRHYDGRTII SEQ ID NO: 82 YKKAFNKSYATFEDE SEQ ID NO: 83 FLESVKYVQSNGGAI SEQ ID NO: 84 IPRGIEYIQHNGWQ SEQ ID NO: 85 IEYIQHNGVVQESYY SEQ ID NO: 86 NACSINGNAPAEIDL SEQ ID NO: 87 RTIIQRDNGYQPNYH SEQ ID NO: 88 EHLKTQFDLNAETNA SEQ ID NO: 89 NGNAPAEIDLRQMRT SEQ ID NO: 90 RGIEYIQHNGVVQES SEQ ID NO: 91 LRQMRTVTPIRMQGG SEQ ID NO: 92 RGIEYIQHNGVVQES SEQ ID NO: 93 IQRDNGYQPNYHAVN SEQ ID NO: 94 IAVIIGIKDLDAFRH SEQ ID NO: 95 IAVIIGIKDLDAFRH SEQ ID NO: 96 ESAYLAYRNQSLDLA SEQ ID NO: 97 GRTIIQRDNGYQPNY SEQ ID NO: 98 TIPRGIEYIQHNGVV SEQ ID NO: 99 GYFAANIDLMMIEEY SEQ ID NO: 100 IPRGIEYIQHNGWQ SEQ ID NO: 101 LDAFRHYDGRTIIQR SEQ ID NO: 102 NKIREALAQTHSAIA SEQ ID NO: 103 RGIEYIQHNGVVQES SEQ ID NO: 104 TNACSINGNAPAEID SEQ ID NO: 105 GYQPNYHAVNIVGYS SEQ ID NO: 106 PRGIEYIQHNGVVQESEQ ID NO: 107 ESVKYVQSNGGAINH SEQ ID NO: 108 PRGIEYIQHNGVVQE SEQ ID NO: 109 RTIIQRDNGYQPNYH SEQ ID NO: 110 TESAYLAYRNQSLDL SEQ ID NO: 111 ATESAYLAYRNQSLD SEQ ID NO: 112 DLRQMRTVTPIRMQG SEQ ID NO: 113 ESVKYVQSNGGAINH SEQ ID NO: 114 ESVKYVQSNGGAINH SEQ ID NO: 115 TFEEYKKAFNKSYAT SEQ ID NO: 116 YQPNYHAVNIVGYSN SEQ ID NO: 117 DGRTIIQRDNGYQPN SEQ ID NO: 118 FNKSYATFEDEEAAR SEQ ID NO: 119 QGVDYWIVRNSWDTN SEQ ID NO: 120 SVKYVQSNGGAINHL SEQ ID NO: 121 FEEYKKAFNKSYATF SEQ ID NO: 122 TIPRGIEYIQHNGVV SEQ ID NO: 123 DLDAFRHYDGRTIIQ SEQ ID NO: 124 AIAVIIGIKDLDAFR SEQ ID NO: 125 AIAVIIGIKDLDAFR SEQ ID NO: 126 SSIKTFEEYKKAFNK SEQ ID NO: 127 GRTIIQRDNGYQPNY SEQ ID NO: 128 GIEYIQHNGVVQESY SEQ ID NO: 129 QPNYHAVNIVGYSNA SEQ ID NO: 130 NKSYATFEDEEAARK SEQ ID NO: 131 NKSYATFEDEEAARK SEQ ID NO: 132 GDNGYGYFAANIDLM SEQ ID NO: 133 NKSYATFEDEEAARK SEQ ID NO: 134 QPNYHAVNIVGYSNA SEQ ID NO: 135 CSINGNAPAEIDLRQ SEQ ID NO: 136 INHLSDLSLDEFKNR SEQ ID NO: 137 SVKYVQSNGGAINHL SEQ ID NO: 138 IKDLDAFRHYDGRTI SEQ ID NO: 139 PRGIEYIQHNGVVQE SEQ ID NO: 140 AVIIGIKDLDAFRHY SEQ ID NO: 141 RGIEYIQHNGVVQES SEQ ID NO: 142 QESYYRYVAREQSCR SEQ ID NO: 143 EYKKAFNKSYATFEDSEQ ID NO: 144 PRGIEYIQHNGVVQE SEQ ID NO: 145 APAEIDLRQMRTVTP SEQ ID NO: 146 EALAQTHSAIAVIIG SEQ ID NO: 147 YQPNYHAVNIVGYSN SEQ ID NO: 148 HLKTQFDLNAETNAC SEQ ID NO: 149 EAFEHLKTQFDLNAE SEQ ID NO: 150 NFLESVKYVQSNGGA SEQ ID NO: 151 DNGYGYFAANIDLMM SEQ ID NO: 152 LESVKYVQSNGGAIN SEQ ID NO: 153 YGYFAANIDLMMIEE SEQ ID NO: 154 PSSIKTFEEYKKAFN SEQ ID NO: 155 GIEYIQHNGWQESY SEQ ID NO: 156 QESYYRYVAREQSCR SEQ ID NO: 157 AATESAYLAYRNQSL SEQ ID NO: 158 KKAFNKSYATFEDEE SEQ ID NO: 159 NGYGYFAANIDLMMI SEQ ID NO: 160 WGDNGYGYFAANIDL SEQ ID NO: 161 LESVKYVQSNGGAIN SEQ ID NO: 162 VVQESYYRYVAREQS SEQ ID NO: 163 ESAYLAYRNQSLDLA SEQ ID NO: 164 LESVKYVQSNGGAIN SEQ ID NO: 165 GVDYWIVRNSWDTNW SEQ ID NO: 166 RQMRTVTPIRMQGGC SEQ ID NO: 167 GYGYFAANIDLMMIE SEQ ID NO: 168 IIGIKDLDAFRHYDG SEQ ID NO: 169 AEAFEHLKTQFDLNA SEQ ID NO: 170 IPRGIEYIQHNGVVQ SEQ ID NO: 171 NIVGYSNAQGVDYWI SEQ ID NO: 172 CWAFSGVAATESAYL SEQ ID NO: 173 PNYHAVNIVGYSNAQ SEQ ID NO: 174 DAFRHYDGRTIIQRD SEQ ID NO: 175 AEAFEHLKTQFDLNA SEQ ID NO: 176 IDLRQMRTVTPIRMQ SEQ ID NO: 177 DGRTIIQRDNGYQPN SEQ ID NO: 178 FNKSYATFEDEEAAR SEQ ID NO: 179 FNKSYATFEDEEAAR SEQ ID NO: 180 TFEEYKKAFNKSYATSEQ ID NO: 181 GYQPNYHAVNIVGYS SEQ ID NO: 182 YQPNYHAVNIVGYSN SEQ ID NO: 183 VVQESYYRYVAREQS SEQ ID NO: 184 ESYYRYVAREQSCRR SEQ ID NO: 185 KTFEEYKKAFNKSYA SEQ ID NO: 186 SNGGAINHLSDLSLD SEQ ID NO: 187 IPRGIEYIQHNGWQ SEQ ID NO: 188 ESAYLAYRNQSLDLA SEQ ID NO: 189 YRYVAREQSCRRPNA SEQ ID NO: 190 IPRGIEYIQHNGWQ SEQ ID NO: 191 AVNIVGYSNAQGVDY SEQ ID NO: 192 DGRTIIQRDNGYQPN SEQ ID NO: 193 VQESYYRYVAREQSC SEQ ID NO: 194 KSYATFEDEEAARKN SEQ ID NO: 195 EYIQHNGVVQESYYR SEQ ID NO: 196 FNKSYATFEDEEAAR SEQ ID NO: 197 FNKSYATFEDEEAAR SEQ ID NO: 198 YYRYVAREQSCRRPN SEQ ID NO: 199 IPRGIEYIQHNGWQ SEQ ID NO: 200 GRTIIQRDNGYQPNY SEQ ID NO: 201 KSYATFEDEEAARKN SEQ ID NO: 202 GIKDLDAFRHYDGRT SEQ ID NO: 203 SAEAFEHLKTQFDLN SEQ ID NO: 204 KAFNKSYATFEDEEA SEQ ID NO: 205 RNSWDTNWGDNGYGY SEQ ID NO: 206 LDAFRHYDGRTIIQR SEQ ID NO: 207 AVIIGIKDLDAFRHY SEQ ID NO: 208 PPNVNKIREALAQTH SEQ ID NO: 209 AQGVDYWIVRNSWDT SEQ ID NO: 210 TIPRGIEYIQHNGW SEQ ID NO: 211 LRQMRTVTPIRMQGG SEQ ID NO: 212 FEEYKKAFNKSYATF SEQ ID NO: 213 ESYYRYVAREQSCRR SEQ ID NO: 214 KDLDAFRHYDGRTII SEQ ID NO: 215 NKSYATFEDEEAARK SEQ ID NO: 216 RGIEYIQHNGWQES SEQ ID NO: 217 VNKIREALAQTHSAISEQ ID NO: 218 RPSSIKTFEEYKKAF SEQ ID NO: 219 EEYKKAFNKSYATFE SEQ ID NO: 220 GYQPNYHAVNIVGYS SEQ ID NO: 221 NVNKIREALAQTHSA SEQ ID NO: 222 NFLESVKYVQSNGGA SEQ ID NO: 223 YKKAFNKSYATFEDE SEQ ID NO: 224 NGYGYFAANIDLMMI SEQ ID NO: 225 AINHLSDLSLDEFKN SEQ ID NO: 226 DGRTIIQRDNGYQPN SEQ ID NO: 227 TIIQRDNGYQPNYHA SEQ ID NO: 228 HAVNIVGYSNAQGVD SEQ ID NO: 229 KSYATFEDEEAARKN SEQ ID NO: 230 VIIGIKDLDAFRHYD SEQ ID NO: 231 GYQPNYHAVNIVGYS SEQ ID NO: 232 LRQMRTVTPIRMQGG SEQ ID NO: 233 SAEAFEHLKTQFDLN SEQ ID NO: 234 VQESYYRYVAREQSC SEQ ID NO: 235 RGIEYIQHNGVVQES SEQ ID NO: 236 SINGNAPAEIDLRQM SEQ ID NO: 237 VRNSWDTNWGDNGYG SEQ ID NO: 238 FLESVKYVQSNGGAI SEQ ID NO: 239 TESAYLAYRNQSLDL SEQ ID NO: 240 KTFEEYKKAFNKSYA SEQ ID NO: 241 PNYHAVNIVGYSNAQ SEQ ID NO: 242 TIIQRDNGYQPNYHA SEQ ID NO: 243 TIPRGIEYIQHNGVV SEQ ID NO: 244 GAINHLSDLSLDEFK SEQ ID NO: 245 KYVQSNGGAINHLSD SEQ ID NO: 246 AFNKSYATFEDEEAA SEQ ID NO: 247 AEAFEHLKTQFDLNA SEQ ID NO: 248 AYLAYRNQSLDLAEQ SEQ ID NO: 249 NGYQPNYHAVNIVGY SEQ ID NO: 250 YHAVNIVGYSNAQGV SEQ ID NO: 251 QESYYRYVAREQSCR SEQ ID NO: 252 AFNKSYATFEDEEAA SEQ ID NO: 253 FSGVAATESAYLAYR SEQ ID NO: 254 GYFAANIDLMMIEEYSEQ ID NO: 255 EYKKAFNKSYATFED SEQ ID NO: 256 VIIGIKDLDAFRHYD SEQ ID NO: 257 DAFRHYDGRTIIQRD SEQ ID NO: 258 HSAIAVIIGIKDLDA SEQ ID NO: 259 YDGRTIIQRDNGYQP SEQ ID NO: 260 ATESAYLAYRNQSLD SEQ ID NO: 261 SYYRYVAREQSCRRP SEQ ID NO: 262 SYATFEDEEAARKNF SEQ ID NO: 263 AFRHYDGRTIIQRDN SEQ ID NO: 264 AFNKSYATFEDEEAA SEQ ID NO: 265 VNIVGYSNAQGVDYW SEQ ID NO: 266 YRYVAREQSCRRPNA SEQ ID NO: 267 INGNAPAEIDLRQMR SEQ ID NO: 268 DTIPRGIEYIQHNGV SEQ ID NO: 269 EHLKTQFDLNAETNA SEQ ID NO: 270 GRTIIQRDNGYQPNY SEQ ID NO: 271 KNRFLMSAEAFEHLK SEQ ID NO: 272 PNYHAVNIVGYSNAQ SEQ ID NO: 273 QGVDYWIVRNSWDTN SEQ ID NO: 274 IIGIKDLDAFRHYDG SEQ ID NO: 275 GIEYIQHNGWQESY SEQ ID NO: 276 SAYLAYRNQSLDLAE SEQ ID NO: 277 NWGDNGYGYFAANID SEQ ID NO: 278 ACSINGNAPAEIDLR SEQ ID NO: 279 VKYVQSNGGAINHLS SEQ ID NO: 280 DNGYGYFAANIDLMM SEQ ID NO: 281 AVNIVGYSNAQGVDY SEQ ID NO: 282 YPPNVNKIREALAQT SEQ ID NO: 283 KSYATFEDEEAARKNSEQ ID NO: 682 TNACSINGNAP SEQ ID NO: 683 TNACSINGNAPA SEQ ID NO: 684 APAEIDLRQMRT SEQ ID NO: 685 EIDLRQMRTVTP SEQ ID NO: 686 EIDLRQMRTVTPI SEQ ID NO: 687 LRQMRTVTPIRM SEQ ID NO: 688 MRTVTPIRMQGGSEQ ID NO: 689 VTPIRMQGGCSEQ ID NO: 690 QGGCGSCWAFSGSEQ ID NO: 691 QGGCGSCWAFSGVAATES SEQ ID NO: 692 CWAFSGVAATESSEQ ID NO: 693 VAATESAYLAYRSEQ ID NO: 694 NQSLDLAEQELVDCASEQ ID NO: 695 NQSLDLAEQELVDCASEQ ID NO: 696 GIEYIQHNGWQESYSEQ ID NO: 697 YIQHNGVVQESYSEQ ID NO: 698 HNGVVQESYYRYSEQ ID NO: 699 HNGVVQESYYRYVARSEQ ID NO: 700 VVQESYYRYVARSEQ ID NO: 701 ESYYRYVAREQSSEQ ID NO: 702 PNAQRFGISNYCQIYPPN SEQ ID NO: 703 QRFGISNYCQIYPPNSEQ ID NO: 704 NYCQIYPPNVNKSEQ ID NO: 705 PNVNKIREALAQTHSEQ ID NO: 706 VNKIREALAQTHSAIASEQ ID NO: 707 ALAQTHSAIAVIIGIKSEQ ID NO: 708 AVIIGIKDLDAFSEQ ID NO: 709 KDLDAFRHYDGRSEQ ID NO: 710 KDLDAFRHYDGRTIISEQ ID NO: 711 DAFRHYDGRTIIQSEQ ID NO: 712 RHYDGRTIIQRDNGYQPN SEQ ID NO: 713 RHYDGRTIIQRDSEQ ID NO: 714 TIIQRDNGYQPNSEQ ID NO: 715 NGYQPNYHAVNISEQ ID NO: 716 QPNYHAVNIVGYSNAQGVDYW SEQ ID NO: 717 YHAVNIVGYSNAQGVSEQ ID NO: 718 VNIVGYSNAQGVSEQ ID NO: 719 VNIVGYSNAQGVDYWSEQ ID NO: 720 VNIVGYSNAQGVDSEQ ID NO: 721 VGYSNAQGVDYWIVRSEQ ID NO: 722 NGYGYFAANIDLMSEQ ID NO: 723 DLMMIEEYPYViii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Der f 1 house dust mite polypeptide (e.g., Der f 1 Isoform 0101), preferably selected from the group consisting of: (a”)-(c”), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a”) SEQ ID NO: 284 (TSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAA TESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQN GWEERSYPYVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREA LTQTHTAIAVIIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVG YGSTQGVDYWI VRNSWDTTWG DSGYGYFQAG N N LM M I EQYPY VVIM);b”) SEQ ID NO: 285 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAE); and c”) SEQ ID NO: 286 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAETSACRINSV NVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAATESAYLAYR NTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQNGWEERSYP YVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREALTQTHTAIAV IIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDYWl VR N SWDTTWG DSGYGYFQAG N N LM M I EQYPYVVI M) ; iv) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 1 -derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1 -derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 287 AVNIVGYGSTQGVDYSEQ ID NO: 288 HAVNIVGYGSTQGVDSEQ ID NO: 289 VNIVGYGSTQGVDYWSEQ ID NO: 290 YHAVNIVGYGSTQGVSEQ ID NO: 291 FSGVAATESAYLAYRSEQ ID NO: 292 DNGYQPNYHAVNIVG SEQ ID NO: 293 HDNGYQPNYHAVNIV SEQ ID NO: 294 PRGIEYIQQNGVVEE SEQ ID NO: 295 PRGIEYIQQNGVVEE SEQ ID NO: 296 AFSGVAATESAYLAY SEQ ID NO: 297 QHDNGYQPNYHAVNI SEQ ID NO: 298 ESAYLAYRNTSLDLS SEQ ID NO: 299 IPRGIEYIQQNGWE SEQ ID NO: 300 IPRGIEYIQQNGWE SEQ ID NO: 301 WAFSGVAATESAYLA SEQ ID NO: 302 SGVAATESAYLAYRN SEQ ID NO: 303 TESAYLAYRNTSLDL SEQ ID NO: 304 NGYQPNYHAVNIVGY SEQ ID NO: 305 LRAFQHYDGRTIIQH SEQ ID NO: 306 ATESAYLAYRNTSLD SEQ ID NO: 307 GRTIIQHDNGYQPNY SEQ ID NO: 308 DLRAFQHYDGRTIIQ SEQ ID NO: 309 IAVIIGIKDLRAFQH SEQ ID NO: 310 YLAYRNTSLDLSEQE SEQ ID NO: 311 TIPRGIEYIQQNGVV SEQ ID NO: 312 QPNYHAVNIVGYGST SEQ ID NO: 313 GIEYIQQNGWEERS SEQ ID NO: 314 RAFQHYDGRTIIQHD SEQ ID NO: 315 DGRTIIQHDNGYQPN SEQ ID NO: 316 IKDLRAFQHYDGRTI SEQ ID NO: 317 GIKDLRAFQHYDGRT SEQ ID NO: 318 RGIEYIQQNGWEER SEQ ID NO: 319 TIPRGIEYIQQNGVV SEQ ID NO: 320 KDLRAFQHYDGRTII SEQ ID NO: 321 YQPNYHAVNIVGYGS SEQ ID NO: 322 IEYIQQNGVVEERSY SEQ ID NO: 323 AIAVIIGIKDLRAFQ SEQ ID NO: 324 NIVGYGSTQGVDYWI SEQ ID NO: 325 RTIIQHDNGYQPNYH SEQ ID NO: 326 PRGIEYIQQNGVVEE SEQ ID NO: 327 LRSLRTVTPIRMQGG SEQ ID NO: 328 IAVIIGIKDLRAFQHSEQ ID NO: 329 SAYLAYRNTSLDLSE SEQ ID NO: 330 RGIEYIQQNGVVEER SEQ ID NO: 331 GRTIIQHDNGYQPNY SEQ ID NO: 332 AYLAYRNTSLDLSEQ SEQ ID NO: 333 QPNYHAVNIVGYGST SEQ ID NO: 334 IQHDNGYQPNYHAVN SEQ ID NO: 335 RGIEYIQQNGVVEER SEQ ID NO: 336 GYQPNYHAVNIVGYG SEQ ID NO: 337 QNGVVEERSYPYVAR SEQ ID NO: 338 QNGVVEERSYPYVAR SEQ ID NO: 339 NYHAVNIVGYGSTQG SEQ ID NO: 340 IREALTQTHTAIAVI SEQ ID NO: 341 DLRSLRTVTPIRMQG SEQ ID NO: 342 LAYRNTSLDLSEQEL SEQ ID NO: 343 QNGVVEERSYPYVAR SEQ ID NO: 344 DGRTIIQHDNGYQPN SEQ ID NO: 345 IGIKDLRAFQHYDGR SEQ ID NO: 346 AIAVIIGIKDLRAFQ SEQ ID NO: 347 REALTQTHTAIAVII SEQ ID NO: 348 DGRTIIQHDNGYQPN SEQ ID NO: 349 AVIIGIKDLRAFQHY SEQ ID NO: 350 LRAFQHYDGRTIIQH SEQ ID NO: 351 AIAVIIGIKDLRAFQ SEQ ID NO: 352 YQPNYHAVNIVGYGS SEQ ID NO: 353 QQNGVVEERSYPYVA SEQ ID NO: 354 QNGVVEERSYPYVAR SEQ ID NO: 355 QIREALTQTHTAIAV SEQ ID NO: 356 YDGRTIIQHDNGYQP SEQ ID NO: 357 IPRGIEYIQQNGVVE SEQ ID NO: 358 ESAYLAYRNTSLDLS SEQ ID NO: 359 RTIIQHDNGYQPNYH SEQ ID NO: 360 GYGYFQAGNNLMMIE SEQ ID NO: 361 DLRAFQHYDGRTIIQ SEQ ID NO: 362 PRGIEYIQQNGVVEE SEQ ID NO: 363 RTIIQHDNGYQPNYH SEQ ID NO: 364 TAIAVIIGIKDLRAF SEQ ID NO: 365 GYGYFQAGNNLMMIESEQ ID NO: 366 QPNYHAVNIVGYGST SEQ ID NO: 367 QGVDYWIVRNSWDTT SEQ ID NO: 368 GRTIIQHDNGYQPNY SEQ ID NO: 369 PRGIEYIQQNGVVEE SEQ ID NO: 370 YQPNYHAVNIVGYGS SEQ ID NO: 371 GIEYIQQNGWEERS SEQ ID NO: 372 RSLRTVTPIRMQGGC SEQ ID NO: 373 GRTIIQHDNGYQPNY SEQ ID NO: 374 QQNGVVEERSYPYVA SEQ ID NO: 375 QQNGVVEERSYPYVA SEQ ID NO: 376 TESAYLAYRNTSLDL SEQ ID NO: 377 ATESAYLAYRNTSLD SEQ ID NO: 378 TAIAVIIGIKDLRAF SEQ ID NO: 379 QPNYHAVNIVGYGST SEQ ID NO: 380 HTAIAVIIGIKDLRA SEQ ID NO: 381 DTIPRGIEYIQQNGV SEQ ID NO: 382 YDGRTIIQHDNGYQP SEQ ID NO: 383 QQNGVVEERSYPYVA SEQ ID NO: 384 LDLRSLRTVTPIRMQ SEQ ID NO: 385 CWAFSGVAATESAYL SEQ ID NO: 386 IQQNGVVEERSYPYV SEQ ID NO: 387 EYIQQNGVVEERSYP SEQ ID NO: 388 PRGIEYIQQNGVVEE SEQ ID NO: 389 GYQPNYHAVNIVGYG SEQ ID NO: 390 LRSLRTVTPIRMQGG SEQ ID NO: 391 IIGIKDLRAFQHYDG SEQ ID NO: 392 RGIEYIQQNGVVEER SEQ ID NO: 393 AVIIGIKDLRAFQHY SEQ ID NO: 394 SAYLAYRNTSLDLSE SEQ ID NO: 395 PNYHAVNIVGYGSTQ SEQ ID NO: 396 GVDYWIVRNSWDTTW SEQ ID NO: 397 IPRGIEYIQQNGVVE SEQ ID NO: 398 YQPNYHAVNIVGYGS SEQ ID NO: 399 IAVIIGIKDLRAFQH SEQ ID NO: 400 RAFQHYDGRTIIQHD SEQ ID NO: 401 SGYGYFQAGNNLMMI SEQ ID NO: 402 DVKQIREALTQTHTASEQ ID NO: 403 VKQIREALTQTHTAI SEQ ID NO: 404 NVPSELDLRSLRTVT SEQ ID NO: 405 IVGYGSTQGVDYWIV SEQ ID NO: 406 GYQPNYHAVNIVGYG SEQ ID NO: 407 DGRTIIQHDNGYQPN SEQ ID NO: 408 TIIQHDNGYQPNYHA SEQ ID NO: 409 SGYGYFQAGNNLMMI SEQ ID NO: 410 TQGVDYWIVRNSWDT SEQ ID NO: 411 NIVGYGSTQGVDYWI SEQ ID NO: 412 SYPYVAREQQCRRPN SEQ ID NO: 413 GYQPNYHAVNIVGYG SEQ ID NO: 414 DSGYGYFQAGNNLMM SEQ ID NO: 415 IPRGIEYIQQNGVVE SEQ ID NO: 416 LRSLRTVTPIRMQGG SEQ ID NO: 417 VNVPSELDLRSLRTV SEQ ID NO: 418 GYGYFQAGNNLMMIE SEQ ID NO: 419 PPDVKQIREALTQTH SEQ ID NO: 420 KDLRAFQHYDGRTII SEQ ID NO: 421 IQQNGVVEERSYPYV SEQ ID NO: 422 YGYFQAGNNLMMIEQ SEQ ID NO: 423 AATESAYLAYRNTSL SEQ ID NO: 424 IIGIKDLRAFQHYDG SEQ ID NO: 425 HTAIAVIIGIKDLRA SEQ ID NO: 426 NGVVEERSYPYVARE SEQ ID NO: 427 TAIAVIIGIKDLRAF SEQ ID NO: 428 VNIVGYGSTQGVDYW SEQ ID NO: 429 NGYQPNYHAVNIVGY SEQ ID NO: 430 RGIEYIQQNGVVEER SEQ ID NO: 431 PRGIEYIQQNGVVEE SEQ ID NO: 432 VIIGIKDLRAFQHYD SEQ ID NO: 433 FSGVAATESAYLAYR SEQ ID NO: 434 RGIEYIQQNGVVEER SEQ ID NO: 435 GIKDLRAFQHYDGRT SEQ ID NO: 436 DLRSLRTVTPIRMQG SEQ ID NO: 437 NGVVEERSYPYVARE SEQ ID NO: 438 YPYVAREQQCRRPNS SEQ ID NO: 439 IKDLRAFQHYDGRTISEQ ID NO: 440 RAFQHYDGRTIIQHDSEQ ID NO: 441 YDGRTIIQHDNGYQPSEQ ID NO: 442 IAVIIGIKDLRAFQHSEQ ID NO: 443 KQIREALTQTHTAIASEQ ID NO: 444 IAVIIGIKDLRAFQHSEQ ID NO: 445 TIPRGIEYIQQNGVVSEQ ID NO: 446 DSGYGYFQAGNNLMMSEQ ID NO: 447 RSYPYVAREQQCRRPSEQ ID NO: 448 PNYHAVNIVGYGSTQv) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 2 house dust mite polypeptide (e.g., Der p 2 Isoform 0110), preferably selected from the group consisting of: (a’”), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a’”) SEQ ID NO: 449 (DQVDVKDCANHEIKKVLVPGCHGSEPCIIHRGKPFQLEAVFEAN QNSKTAKI El KASI DGLEVDVPGI DPNACHYM KCPLVKGQQYDI K YTWNVPKIAPKSENVWTVKVMGDNGVLACAIATHAKIRD); vi) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 2-derived HLA-binding peptides (e.g., as depicted in Tables 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA- DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NO: 450 LEAVFEANQNSKTAKSEQ ID NO: 451 EAVFEANQNSKTAKISEQ ID NO: 452 QLEAVFEANQNSKTASEQ ID NO: 453 DIKYTWNVPKIAPKSSEQ ID NO: 454 YDIKYTWNVPKIAPKSEQ ID NO: 455 AVFEANQNSKTAKIESEQ ID NO: 456 QYDIKYTWNVPKIAPSEQ ID NO: 457 IKYTWNVPKIAPKSESEQ ID NO: 458 KASIDGLEVDVPGID SEQ ID NO: 459 FQLEAVFEANQNSKT SEQ ID NO: 460 QYDIKYTWNVPKIAP SEQ ID NO: 461 VFEANQNSKTAKIEI SEQ ID NO: 462 IKASIDGLEVDVPGI SEQ ID NO: 463 IDGLEVDVPGIDPNA SEQ ID NO: 464 KYTWNVPKIAPKSEN SEQ ID NO: 465 QQYDIKYTWNVPKIA SEQ ID NO: 466 SIDGLEVDVPGIDPN SEQ ID NO: 467 QQYDIKYTWNVPKIA SEQ ID NO: 468 YDIKYTWNVPKIAPK SEQ ID NO: 469 IDGLEVDVPGIDPNA SEQ ID NO: 470 GKPFQLEAVFEANQN SEQ ID NO: 471 EIKASIDGLEVDVPG SEQ ID NO: 472 GKPFQLEAVFEANQN SEQ ID NO: 473 VVVTVKVMGDNGVLA SEQ ID NO: 474 ASIDGLEVDVPGIDP SEQ ID NO: 475 DGLEVDVPGIDPNAC SEQ ID NO: 476 SIDGLEVDVPGIDPN SEQ ID NO: 477 GQQYDIKYTWNVPKI SEQ ID NO: 478 GKPFQLEAVFEANQN SEQ ID NO: 479 DIKYTWNVPKIAPKS SEQ ID NO: 480 LEAVFEANQNSKTAK SEQ ID NO: 481 RGKPFQLEAVFEANQ SEQ ID NO: 482 EAVFEANQNSKTAKI SEQ ID NO: 483 PKSENVVVTVKVMGD SEQ ID NO: 484 ASIDGLEVDVPGIDP SEQ ID NO: 485 VPKIAPKSENVVVTV SEQ ID NO: 486 LEAVFEANQNSKTAK SEQ ID NO: 487 DGLEVDVPGIDPNAC SEQ ID NO: 488 VTVKVMGDNGVLACA SEQ ID NO: 489 TAKIEIKASIDGLEV SEQ ID NO: 490 VTVKVMGDNGVLACA SEQ ID NO: 491 TVKVMGDNGVLACAI SEQ ID NO: 492 TVKVMGDNGVLACAI SEQ ID NO: 493 NVPKIAPKSENVVVT SEQ ID NO: 494 RGKPFQLEAVFEANQSEQ ID NO: 495 RGKPFQLEAVFEANQ SEQ ID NO: 496 EAVFEANQNSKTAKI SEQ ID NO: 497 GKPFQLEAVFEANQN SEQ ID NO: 498 QYDIKYTWNVPKIAP SEQ ID NO: 499 ASIDGLEVDVPGIDP SEQ ID NO: 500 SENVVVTVKVMGDNG SEQ ID NO: 501 KTAKIEIKASIDGLE SEQ ID NO: 502 VPGIDPNACHYMKCP SEQ ID NO: 503 APKSENVVVTVKVMG SEQ ID NO: 504 DIKYTWNVPKIAPKS SEQ ID NO: 505 VVTVKVMGDNGVLAC SEQ ID NO: 506 QLEAVFEANQNSKTA SEQ ID NO: 507 GQQYDIKYTWNVPKI SEQ ID NO: 508 YDIKYTWNVPKIAPK SEQ ID NO: 509 KGQQYDIKYTWNVPK SEQ ID NO: 510 QYDIKYTWNVPKIAP SEQ ID NO: 511 DIKYTWNVPKIAPKS SEQ ID NO: 512 VDVPGIDPNACHYMK SEQ ID NO: 513 KSENVVVTVKVMGDN SEQ ID NO: 514 RGKPFQLEAVFEANQ SEQ ID NO: 515 KGQQYDIKYTWNVPK SEQ ID NO: 516 VVTVKVMGDNGVLAC SEQ ID NO: 517 YDIKYTWNVPKIAPK SEQ ID NO: 518 NVVVTVKVMGDNGVL SEQ ID NO: 519 VVVTVKVMGDNGVLA SEQ ID NO: 520 IDGLEVDVPGIDPNA SEQ ID NO: 521 QQYDIKYTWNVPKIA SEQ ID NO: 522 IKYTWNVPKIAPKSE SEQ ID NO: 523 VVTVKVMGDNGVLAC SEQ ID NO: 524 WNVPKIAPKSENVVV SEQ ID NO: 525 KASIDGLEVDVPGID SEQ ID NO: 526 GKPFQLEAVFEANQN SEQ ID NO: 527 IAPKSENVVVTVKVM SEQ ID NO: 528 KSENVVVTVKVMGDN SEQ ID NO: 529 KPFQLEAVFEANQNS SEQ ID NO: 530 SENVVVTVKVMGDNG SEQ ID NO: 531 PKIAPKSENVVVTVKSEQ ID NO: 532 GQQYDIKYTWNVPKISEQ ID NO: 533 QQYDIKYTWNVPKIASEQ ID NO: 534 DVPGIDPNACHYMKCSEQ ID NO: 724 DQVDVKDCANHEIKKSEQ ID NO: 725 HGSEPCIIHRGKSEQ ID NO: 726 HGSEPCIIHRGKSEQ ID NO: 727 HGSEPCIIHRGKPFQSEQ ID NO: 728 HGSEPCIIHRGKPFQLEASEQ ID NO: 729 EPCIIHRGKPFQLEASEQ ID NO: 730 EPCIIHRGKPFQLEALFESEQ ID NO: 731 LEALFEANQNTKNAKSEQ ID NO: 732 LEALFEANQNTKNAKSEQ ID NO: 733 LEALFEANQNTKNAKSEQ ID NO: 734 LEALFEANQNTKNAKIEIKASIDG (+49-60Epitop corresponding to SEQ ID NO: 748) SEQ ID NO: 735 LFEANQNTKNAKSEQ ID NO: 736 NTKNAKIEIKASSEQ ID NO: 737 DVPGIDPNACHYVKCPLVKGQSEQ ID NO: 738 GIDPNACHYVKCPLVSEQ ID NO: 739 PNACHYVKCPLVKGQSEQ ID NO: 740 QYDIKYTWNVPKIAPSEQ ID NO: 741 VPKIAPKSENVVSEQ ID NO: 742 VPKIAPKSENVVVTVKVLSEQ ID NO: 743 GVLACAIATHAKvii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 2 house dust mite polypeptide (e.g., Der f 2 Isoform 0102), preferably selected from the group consisting of: (a””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a””) SEQ ID NO: 535 (DQVDVKDCANNEIKKVMVDGCHGSDPCIIHRGKPFTLEALFDAN QNTKTAKIEIKASLDGLEIDVPGIDTNACHFMKCPLVKGQQYDIKY TWNVPKIAPKSENVWTVKLIGDNGVLACAIATHGKIRD);viii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 2-derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 536 LEALFDANQNTKTAKSEQ ID NO: 537 EALFDANQNTKTAKISEQ ID NO: 538 DIKYTWNVPKIAPKSSEQ ID NO: 539 YDIKYTWNVPKIAPKSEQ ID NO: 540 TLEALFDANQNTKTASEQ ID NO: 541 QYDIKYTWNVPKIAPSEQ ID NO: 542 ALFDANQNTKTAKIESEQ ID NO: 543 IKYTWNVPKIAPKSESEQ ID NO: 544 NNEIKKVMVDGCHGSSEQ ID NO: 545 ANNEIKKVMVDGCHGSEQ ID NO: 546 QYDIKYTWNVPKIAPSEQ ID NO: 547 KASLDGLEIDVPGIDSEQ ID NO: 548 KYTWNVPKIAPKSENSEQ ID NO: 549 QQYDIKYTWNVPKIASEQ ID NO: 550 QQYDIKYTWNVPKIASEQ ID NO: 551 CANNEIKKVMVDGCHSEQ ID NO: 552 VTVKLIGDNGVLACASEQ ID NO: 553 LDGLEIDVPGIDTNASEQ ID NO: 554 NEIKKVMVDGCHGSDSEQ ID NO: 555 YDIKYTWNVPKIAPKSEQ ID NO: 556 FTLEALFDANQNTKTSEQ ID NO: 557 TVKLIGDNGVLACAISEQ ID NO: 558 SLDGLEIDVPGIDTNSEQ ID NO: 559 LDGLEIDVPGIDTNASEQ ID NO: 560 TVKLIGDNGVLACAISEQ ID NO: 561 VTVKLIGDNGVLACASEQ ID NO: 562 IKASLDGLEIDVPGISEQ ID NO: 563 LFDANQNTKTAKIEISEQ ID NO: 564 VVTVKLIGDNGVLACSEQ ID NO: 565 GQQYDIKYTWNVPKISEQ ID NO: 566 DGLEIDVPGIDTNAC SEQ ID NO: 567 SLDGLEIDVPGIDTN SEQ ID NO: 568 DIKYTWNVPKIAPKS SEQ ID NO: 569 VWTVKLIGDNGVLA SEQ ID NO: 570 ASLDGLEIDVPGIDT SEQ ID NO: 571 VPKIAPKSENVVVTV SEQ ID NO: 572 PKSENVVVTVKLIGD SEQ ID NO: 573 NVPKIAPKSENVVVT SEQ ID NO: 574 DGLEIDVPGIDTNAC SEQ ID NO: 575 TVKLIGDNGVLACAI SEQ ID NO: 576 VVTVKLIGDNGVLAC SEQ ID NO: 577 VWTVKLIGDNGVLA SEQ ID NO: 578 EIKASLDGLEIDVPG SEQ ID NO: 579 EIKKVMVDGCHGSDP SEQ ID NO: 580 SENVVVTVKLIGDNG SEQ ID NO: 581 QYDIKYTWNVPKIAP SEQ ID NO: 582 GKPFTLEALFDANQN SEQ ID NO: 583 VTVKLIGDNGVLACA SEQ ID NO: 584 VKLIGDNGVLACAIA SEQ ID NO: 585 TAKIEIKASLDGLEI SEQ ID NO: 586 KSENVVVTVKLIGDN SEQ ID NO: 587 DIKYTWNVPKIAPKS SEQ ID NO: 588 KTAKIEIKASLDGLE SEQ ID NO: 589 VKLIGDNGVLACAIA SEQ ID NO: 590 GQQYDIKYTWNVPKI SEQ ID NO: 591 YDIKYTWNVPKIAPK SEQ ID NO: 592 KGQQYDIKYTWNVPK SEQ ID NO: 593 QYDIKYTWNVPKIAP SEQ ID NO: 594 DIKYTWNVPKIAPKS SEQ ID NO: 595 ASLDGLEIDVPGIDT SEQ ID NO: 596 LEALFDANQNTKTAK SEQ ID NO: 597 EALFDANQNTKTAKI SEQ ID NO: 598 SENVVVTVKLIGDNG SEQ ID NO: 599 APKSENVVVTVKLIG SEQ ID NO: 600 KGQQYDIKYTWNVPK SEQ ID NO: 601 EIKKVMVDGCHGSDP SEQ ID NO: 602 YDIKYTWNVPKIAPKSEQ ID NO: 603 QQYDIKYTWNVPKIASEQ ID NO: 604 RGKPFTLEALFDANQSEQ ID NO: 605 IKYTWNVPKIAPKSESEQ ID NO: 606 WNVPKIAPKSENVVVSEQ ID NO: 607 ASLDGLEIDVPGIDTSEQ ID NO: 608 LEALFDANQNTKTAKSEQ ID NO: 609 VVVTVKLIGDNGVLASEQ ID NO: 610 KSENVVVTVKLIGDNSEQ ID NO: 611 IKKVMVDGCHGSDPCSEQ ID NO: 612 PKIAPKSENVVVTVKSEQ ID NO: 613 KASLDGLEIDVPGIDSEQ ID NO: 614 VKLIGDNGVLACAIASEQ ID NO: 615 ENVVVTVKLIGDNGVSEQ ID NO: 616 GQQYDIKYTWNVPKISEQ ID NO: 617 QQYDIKYTWNVPKIASEQ ID NO: 618 ENVVVTVKLIGDNGVSEQ ID NO: 619 NEIKKVMVDGCHGSDSEQ ID NO: 620 PKSENVVVTVKLIGDix) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 23 house dust mite polypeptide (e.g., Der p 23 Isoform 0101) selected from the group consisting of: (a’””), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01:a’””) SEQ ID NO: 621 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT);x)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 622 SRFGYFADPKDPHKFSEQ ID NO: 623 RFGYFADPKDPHKFYSEQ ID NO: 624 PSRFGYFADPKDPHKSEQ ID NO: 625 RFGYFADPKDPHKFYSEQ ID NO: 626 SRFGYFADPKDPHKFSEQ ID NO: 627 PSRFGYFADPKDPHKSEQ ID NO: 628 PHKFYICSNWEAVHKSEQ ID NO: 629 FGYFADPKDPHKFYISEQ ID NO: 630 FGYFADPKDPHKFYISEQ ID NO: 631 PHKFYICSNWEAVHKSEQ ID NO: 632 CPSRFGYFADPKDPHSEQ ID NO: 633 RFGYFADPKDPHKFYSEQ ID NO: 634 PSRFGYFADPKDPHKSEQ ID NO: 635 SRFGYFADPKDPHKFSEQ ID NO: 636 DPHKFYICSNWEAVHSEQ ID NO: 637 CPSRFGYFADPKDPHSEQ ID NO: 638 DPHKFYICSNWEAVHSEQ ID NO: 639 PSRFGYFADPKDPHKSEQ ID NO: 640 HKFYICSNWEAVHKDSEQ ID NO: 641 PSRFGYFADPKDPHKSEQ ID NO: 642 PSRFGYFADPKDPHKSEQ ID NO: 643 GYFADPKDPHKFYICSEQ ID NO: 644 GYFADPKDPHKFYICSEQ ID NO: 645 PHKFYICSNWEAVHKSEQ ID NO: 646 PHKFYICSNWEAVHKSEQ ID NO: 647 I I I VHPTTTEQPDDKxi) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 23 house dust mite polypeptide (e.g., Der f 23 Isoform 0201), preferably selected from the group consisting of: (a”””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01:a”””) SEQ ID NO: 648 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT);andSEQ ID NO: 744 (DIDHDDDPTTMIDVQTTTVQPSDEFECPT RFGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT); xii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 649 TTMIDVQ I I I VQPSDSEQ ID NO: 650 PTTMIDVQ I I I VORSSEQ ID NO: 651 TMIDVQI I I VQPSDESEQ ID NO: 652 DPTTMIDVQ I I I VQPSEQ ID NO: 653 RFGYFADPKDPCKFYSEQ ID NO: 654 TRFGYFADPKDPCKFSEQ ID NO: 655 PTRFGYFADPKDPCKSEQ ID NO: 656 MIDVQ I I I VQPSDEFSEQ ID NO: 657 RFGYFADPKDPCKFYSEQ ID NO: 658 TRFGYFADPKDPCKFSEQ ID NO: 659 FGYFADPKDPCKFYISEQ ID NO: 660 PTRFGYFADPKDPCKSEQ ID NO: 661 PTTMIDVQ I I I VORSSEQ ID NO: 662 RFGYFADPKDPCKFYSEQ ID NO: 663 DPTTMIDVQ I I I VQPSEQ ID NO: 664 CPTRFGYFADPKDPCSEQ ID NO: 665 TRFGYFADPKDPCKFSEQ ID NO: 666 PTRFGYFADPKDPCKSEQ ID NO: 667 IDVQTTTVQPSDEFESEQ ID NO: 668 FGYFADPKDPCKFYISEQ ID NO: 669 TMIDVQI I I VQPSDESEQ ID NO: 670 DDPTTMIDVQI I I VQSEQ ID NO: 671 PCKFYICSNWEAIHKSEQ ID NO: 672 MIDVQ I I I VQPSDEFc) optionally, one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673 (GGGGS);d) one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) transmembrane domains (e.g., derived from LAMP-1 (e.g., having Uniprot accession numbers: P11438 or P11279), LAMP-2 (e.g., having Uniprot accession number: P13473), HLA class II histocompatibility antigen gamma chain (e.g., having Uniprot accession number: P04233), HLA class I histocompatibility antigen, A alpha chain (e.g., having Uniprot accession number: P04439), HLA class I histocompatibility antigen, B alpha chain (e.g., having Uniprot accession number: P01889), HLA class I histocompatibility antigen, C alpha chain (e.g., having Uniprot accession number: P10321) and / or Transferrin receptor protein 1 (e.g., having Uniprot accession number: P02786) and one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) cytosolic domains (e.g., derived from LAMP-1 (e.g., having Uniprot accession numbers: P11438 or P11279), LAMP-2 (e.g., having Uniprot accession number: P13473), HLA class II histocompatibility antigen gamma chain (e.g., having Uniprot accession number: P04233), HLA class I histocompatibility antigen, A alpha chain (e.g., having Uniprot accession number: P04439), HLA class I histocompatibility antigen, B alpha chain (e.g., having Uniprot accession number: P01889), HLA class I histocompatibility antigen, C alpha chain (e.g., having Uniprot accession number: P10321) and / or Transferrin receptor protein 1 (e.g., having Uniprot accession number: P02786); preferably said one or more transmembrane domains and one or more cytosolic domains comprising or consisting of the human SEQ ID NO: 674 (MLIPIAVGGALAGLVLIVLIAYLVGRKRSHAGYQTI) and / or murine SEQ ID NO: 675 (MLIPIAVGGALAGLVLIVLIAYLIGRKRSHAGYQTI).A polypeptide comprising or consisting of the following sequence (b) and, optionally, one or more of the following sequences (a), (c), and / or (d), preferably in the following order: (a) a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1 , further preferably the polypeptide fragment is at least 15 amino acids long, even further preferably the signal polypeptide has at least 75% sequence identity to SEQ ID NO:1 or SEQ ID NO: 2, most preferably said signal polypeptide comprises or consists of the human SEQ ID NO: 1 or the murine SEQ ID NO: 2;(b) one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides, preferably allergens, selected from the group consisting of (i)-(vii) :i) a polypeptide comprising or consisting of one or more Derp 1-derived HLA- binding peptides, wherein said one or more Der p 1-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 6-283; 682-723; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01;HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 4, and SEQ ID NO: 3;ii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite-derived polypeptide of SEQ ID NO: 285, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01;iii) a polypeptide comprising or consisting of one or more Der f 1 -derived H LA- binding peptides, wherein said one or more Der f 1-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 287-448; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 1 dust mite polypeptide selected from the group consisting of SEQ ID NO: 284 and SEQ ID NO: 286;iv) a polypeptide comprising or consisting of one or more Der p 2-derived HLA- binding peptides, wherein said one or more Der p 2-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 450-534; 724-743; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449;v) a polypeptide comprising or consisting of one or more Der f 2-derived HLA- binding peptides, wherein said one or more Der f 2-derived HLA-binding peptides are selected from the group consisting of: SEQ ID NOs: 536-620; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide of SEQ ID NO: 535;vi) a polypeptide comprising or consisting of one or more Der p 23-derived HLA-binding peptides, wherein said one or more Der p 23-derived HLA- binding peptides are selected from the group consisting of: SEQ ID NOs: 622-647; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621;vii) a polypeptide comprising or consisting of one or more Der f 23-derived HLA-binding peptides, wherein said one or more Der f 23-derived HLA- binding peptides are selected from the group consisting of: SEQ ID NOs: 649-672; preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA- DRB5*01:01; preferably, said polypeptide is a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NOs: 648 or 744;(c) one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673;(d) one or more transmembrane domains and one or more cytosolic domains, preferably in the following order:d’) one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; andd”) one or more cytosolic domains, preferably derived from LAMP-1 , LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1;preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) have a sequence identity of at least 75% to SEQ ID NO: 674 or murine SEQ ID NO: 675; further preferably, said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) comprising or consisting of the human SEQ ID NO: 674 or murine SEQ ID NO: 675.The polypeptide of any one of the preceding items, wherein said polypeptide comprising or consisting of a polypeptide selected from the group consisting of:SEQ ID NO: 676 MAAPGARRPLLLLLLAGLAHGASARPSSIKTFEEYKKAFNKSY ATFEDEEAARKNFLESVKYVQSNGGAINHLSDLSLDEFKNRFL MSAEAFEHLKTQFDLNAETNACSINGNAPAEIDLRQMRTVTPI RMQGGCGSCWAFSGVAATESAYLAYRNQSLDLAEQELVDCA SQHGCHGDTIPRGIEYIQHNGWQESYYRYVAREQSCRRPNA QRFGISNYCQIYPPNVNKIREALAQTHSAIAVIIGIKDLDAFRHY DGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYWIVRNSWDTN WGDNGYGYFAANIDLMMIEEYPYVVILGGGGSMLIPIAVGGAL AGLVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 677 MAAPGARRPLLLLLLAGLAHGASARPASIKTFEEFKKAFNKNY ATVEEEEVARKNFLESLKYVEANKGAINHLSDLSLDEFKNRYL MSAEAFEQLKTQFDLNAETSACRINSVNVPSELDLRSLRTVTP IRMQGGCGSCWAFSGVAATESAYLAYRNTSLDLSEQELVDCA SQHGCHGDTIPRGIEYIQQNGVVEERSYPYVAREQQCRRPNS QHYGISNYCQIYPPDVKQIREALTQTHTAIAVIIGIKDLRAFQHY DGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDYWIVRNSWDTT WGDSGYGYFQAG N N LM M 1 EQYPYVVI MGGGGSM LI PI AVGG ALAGLVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 678 MAAPGARRPLLLLLLAGLAHGASADQVDVKDCANHEIKKVLV PGCHGSEPCIIHRGKPFQLEAVFEANQNSKTAKIEIKASIDGLE VDVPGI DPNACHYM KCPLVKGQQYDI KYTWN VPKIAPKSEN V VVTVKVMGDNGVLACAIATHAKIRDGGGGSMLIPIAVGGALAG LVLIVLIAYLIGRKRSHAGYQTISEQ ID NO: 679 MAAPGARRPLLLLLLAGLAHGASADQVDVKDCANNEIKKVMV DGCHGSDPCIIHRGKPFTLEALFDANQNTKTAKIEIKASLDGLE1 DVPGI DTNACH FM KCPLVKGQQYDI KYTWN VPKIAPKSEN VV VTVKLIGDNGVLACAIATHGKIRDGGGGSMLIPIAVGGALAGLV LIVLIAYLIGRKRSHAGYQTISEQ ID NO: 680 MAAPGARRPLLLLLLAGLAHGASAANDNDDDP 1 1 I VHPI’TTE QPDDKFECPSRFGYFADPKDPHKFYICSNWEAVHKDCPGNT RWNEDEETCTGGGGSMLIPIAVGGALAGLVLIVLIAYLIGRKRS HAGYQTISEQ ID NO: 681 MAAPGARRPLLLLLLAGLAHGASADIDHDDDPTTMIDVQ I I I V QPSDEFECPTRFGYFADPKDPCKFYICSNWEAIHKSCPGNTR WNEKELTCTGGGGSMLIPIAVGGALAGLVLIVLIAYLIGRKRSH AGYQTIor wherein said polypeptide comprising or consisting of a polypeptide selected from the group consisting of: SEQ ID NOs: 749, 751, 753, 755, 757 and 759 (e.g., as shown in Examples 3-4 herein).A cell (e.g., a host cell, preferably a recombinant and / or isolated host cell), plurality of said cells (e.g., recombinant and / or isolated plurality), lipid nanoparticles (LNPs) or polymersomes comprising and / or expressing one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the nucleic acid construct / s and / or the one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the polypeptides of any one of the preceding items, preferably said cell or plurality of cells is prokaryotic (e.g., bacterial cell / plurality of cells) or eukaryotic (e.g., mammalian cell / plurality of cells).One or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) polypeptides of any one of the preceding items, wherein said one or more polypeptides are obtained (e.g., translated) from / by the nucleic acid construct, cell, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of any one of the preceding items, preferably said obtained comprises synthesising via an in vitro transcription (IVT).A composition comprising one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the nucleic acid construct / s, polypeptide / s, cell / s, plurality of cells, LNPs and / or polymersomes of any one of preceding items.The composition of any one of the preceding items, wherein said composition is a diagnostic, pharmaceutical composition, immune-therapeutical, allergen immunotherapy (AIT) composition, in vitro transcription (i.e., IVT composition) composition, delivery composition and / or vaccine composition, preferably said vaccine composition is selected from a mRNA- and viral vaccine composition.The composition of any one of the preceding items, wherein said composition is an immune-therapeutical composition.The composition of any one of the preceding items, wherein said composition is a vaccine. The composition of any one of the preceding items, wherein said composition is a vaccine composition comprising one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) mRNAs constructs and / or one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) polypeptides of any one of the preceding items.A method for treatment, amelioration and / or prophylaxis of allergy, preferably in a subject, said method comprising administering a therapeutically effective amount of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the nucleic acid constructs, the polypeptide, composition, cell, plurality of cells, LNPs and / or polymersomes of any one of preceding items to a subject in need thereof.A method for increasing tolerance to dust mites, preferably in a subject, said method comprising administering a therapeutically effective amount of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the nucleic acid constructs, the polypeptide, composition, cell, plurality of cells, LNPs and / or polymersomes of any one of preceding items to a subject in need thereof.A method for reducing a serum allergen-specific IgE level, preferably in a subject, said method comprising administering a therapeutically effective amount of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) of the nucleic acid constructs, the polypeptide, composition, cell, plurality of cells, LNPs and / or polymersomes of any one of preceding items to a subject in need thereof.The method of any one of the preceding items, wherein the subject is a mammal, preferably a human.The method of any one of the preceding items, wherein the subject has an allergy, preferably a dust mite allergy.The method of any one of the preceding items, wherein the subject has an allergic rhinitis, preferably an allergic rhinitis is caused by a house dust mite.The method of any one of the preceding items, wherein the subject has one or more conditions selected from the group consisting of:a) Eczema (atopic dermatitis);b) Asthma;c) Sinusitis;d) Conjunctivitis; ande) Sleep disorder;f) preferably said one or more conditions (a)-(e) are caused by or associated with a house dust mite.The method of any one of the preceding items, wherein the subject has one or more symptoms selected from the group consisting of:a) Respiratory symptoms, preferably comprising one or more of the following:sneezing, runny or stuffy nose, postnasal drip; further preferably selected from the group consisting of: sneezing, runny or stuffy nose, postnasal drip; b) Asthma symptoms, preferably comprising one or more of the following:wheezing, coughing and shortness of breath, further preferably selected from the group consisting of: wheezing, coughing and shortness of breath;c) Ocular symptoms, preferably comprising one or more of the following: itchy and / or watery eyes, further preferably selected from the group consisting of: itchy and / or watery eyes;d) Skin symptoms, preferably comprising one or more of the following: eczema; e) Fatigue; andf) Headache;g) Preferably said one or more symptoms (a)-(f) are caused by or associated with a house dust mite.The method of any one of the preceding items, wherein the subject has a serum allergenspecific lgE>0.35 kll / L against an allergen derived from the dust mites.The method of any one of the preceding items, wherein the serum allergen-specific IgE level is reduced by at least 20% from baseline following administration.The method of any one of the preceding items, wherein the serum allergen-specific IgE level is reduced by at least 5000 from baseline following administration.The method of any one of the preceding items, wherein the allergen is selected from the group consisting of:a) one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides (e.g., as depiczed in Example 1 (e.g., as depicted in Figure 1) and / or 2 and / or Example 3 and / or Example 4 herein, e.g., as in Table 2 and / or 3 herein), preferably selected from the group consisting of:i) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Der p 1 house dust mite polypeptide (e.g., Der p 1 Isoform 0102), preferably selected from the group consisting of: (a’)-(c’), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA- DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA- DRB5*01:01:a’) SEQ ID NO: 3 (TNACSINGNAPAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAAT ESAYLAYRNQSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNG VVQESYYRYVAREQSCRRPNAQRFGISNYCQIYPPNVNKIREAL AQTHSAIAVIIGIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGY SNAQGVDYWIVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYW IL);b’) SEQ ID NO: 4 (RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAE); andc) SEQ ID NO: 5 (RPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVKYVQSNGG AINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAETNACSINGN APAEIDLRQMRTVTPIRMQGGCGSCWAFSGVAATESAYLAYRN QSLDLAEQELVDCASQHGCHGDTIPRGIEYIQHNGWQESYYRY VAREQSCRRPNAQRFGISNYCQIYPPNVNKIREALAQTHSAIAVII GIKDLDAFRHYDGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYW IVRNSWDTNWGDNGYGYFAANIDLMMIEEYPYWIL); ii) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 1-derived HLA-binding peptides (e.g., as in Table 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA- DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA- binding peptides selected from the group consisting of:SEQ ID NO: 6 HAVNIVGYSNAQGVDSEQ ID NO: 7 AVNIVGYSNAQGVDYSEQ ID NO: 8 YHAVNIVGYSNAQGVSEQ ID NO: 9 VNIVGYSNAQGVDYWSEQ ID NO: 10 ESVKYVQSNGGAINHSEQ ID NO: 11 SVKYVQSNGGAINHLSEQ ID NO: 12 LESVKYVQSNGGAINSEQ ID NO: 13 SYATFEDEEAARKNFSEQ ID NO: 14 YATFEDEEAARKNFLSEQ ID NO: 15 YLAYRNQSLDLAEQESEQ ID NO: 16 AYLAYRNQSLDLAEQSEQ ID NO: 17 LAYRNQSLDLAEQELSEQ ID NO: 18 FSGVAATESAYLAYRSEQ ID NO: 19 KSYATFEDEEAARKNSEQ ID NO: 20 DNGYQPNYHAVNIVGSEQ ID NO: 21 DLSLDEFKNRFLMSASEQ ID NO: 22 RDNGYQPNYHAVNIVSEQ ID NO: 23 ESAYLAYRNQSLDLASEQ ID NO: 24 SAYLAYRNQSLDLAESEQ ID NO: 25 AFSGVAATESAYLAYSEQ ID NO: 26 ATFEDEEAARKNFLESEQ ID NO: 27 TESAYLAYRNQSLDLSEQ ID NO: 28 SVKYVQSNGGAINHL SEQ ID NO: 29 IREALAQTHSAIAVI SEQ ID NO: 30 VKYVQSNGGAINHLS SEQ ID NO: 31 VKYVQSNGGAINHLS SEQ ID NO: 32 ESVKYVQSNGGAINH SEQ ID NO: 33 ATESAYLAYRNQSLD SEQ ID NO: 34 QRDNGYQPNYHAVNI SEQ ID NO: 35 SDLSLDEFKNRFLMS SEQ ID NO: 36 LDAFRHYDGRTIIQR SEQ ID NO: 37 PRGIEYIQHNGVVQE SEQ ID NO: 38 NIVGYSNAQGVDYWI SEQ ID NO: 39 KIREALAQTHSAIAV SEQ ID NO: 40 NYHAVNIVGYSNAQG SEQ ID NO: 41 WAFSGVAATESAYLA SEQ ID NO: 42 REALAQTHSAIAVII SEQ ID NO: 43 SGVAATESAYLAYRN SEQ ID NO: 44 FLESVKYVQSNGGAI SEQ ID NO: 45 FEHLKTQFDLNAETN SEQ ID NO: 46 NGYQPNYHAVNIVGY SEQ ID NO: 47 DLDAFRHYDGRTIIQ SEQ ID NO: 48 PSSIKTFEEYKKAFN SEQ ID NO: 49 IPRGIEYIQHNGWQ SEQ ID NO: 50 DAFRHYDGRTIIQRD SEQ ID NO: 51 AVNIVGYSNAQGVDY SEQ ID NO: 52 ACSINGNAPAEIDLR SEQ ID NO: 53 LESVKYVQSNGGAIN SEQ ID NO: 54 SAYLAYRNQSLDLAE SEQ ID NO: 55 PRGIEYIQHNGVVQE SEQ ID NO: 56 YGYFAANIDLMMIEE SEQ ID NO: 57 RPSSIKTFEEYKKAF SEQ ID NO: 58 KKAFNKSYATFEDEE SEQ ID NO: 59 QPNYHAVNIVGYSNA SEQ ID NO: 60 NAPAEIDLRQMRTVT SEQ ID NO: 61 KTQFDLNAETNACSI SEQ ID NO: 62 AYRNQSLDLAEQELV SEQ ID NO: 63 LKTQFDLNAETNACS SEQ ID NO: 64 GNAPAEIDLRQMRTVSEQ ID NO: 65 PRGIEYIQHNGVVQE SEQ ID NO: 66 VNIVGYSNAQGVDYW SEQ ID NO: 67 YQPNYHAVNIVGYSN SEQ ID NO: 68 GGAINHLSDLSLDEF SEQ ID NO: 69 HAVNIVGYSNAQGVD SEQ ID NO: 70 LESVKYVQSNGGAIN SEQ ID NO: 71 NGGAINHLSDLSLDE SEQ ID NO: 72 LSDLSLDEFKNRFLM SEQ ID NO: 73 GYGYFAANIDLMMIE SEQ ID NO: 74 KYVQSNGGAINHLSD SEQ ID NO: 75 AFEHLKTQFDLNAET SEQ ID NO: 76 NKSYATFEDEEAARK SEQ ID NO: 77 GIEYIQHNGWQESY SEQ ID NO: 78 QPNYHAVNIVGYSNA SEQ ID NO: 79 LSLDEFKNRFLMSAE SEQ ID NO: 80 NKSYATFEDEEAARK SEQ ID NO: 81 KDLDAFRHYDGRTII SEQ ID NO: 82 YKKAFNKSYATFEDE SEQ ID NO: 83 FLESVKYVQSNGGAI SEQ ID NO: 84 IPRGIEYIQHNGWQ SEQ ID NO: 85 IEYIQHNGVVQESYY SEQ ID NO: 86 NACSINGNAPAEIDL SEQ ID NO: 87 RTIIQRDNGYQPNYH SEQ ID NO: 88 EHLKTQFDLNAETNA SEQ ID NO: 89 NGNAPAEIDLRQMRT SEQ ID NO: 90 RGIEYIQHNGVVQES SEQ ID NO: 91 LRQMRTVTPIRMQGG SEQ ID NO: 92 RGIEYIQHNGVVQES SEQ ID NO: 93 IQRDNGYQPNYHAVN SEQ ID NO: 94 IAVIIGIKDLDAFRH SEQ ID NO: 95 IAVIIGIKDLDAFRH SEQ ID NO: 96 ESAYLAYRNQSLDLA SEQ ID NO: 97 GRTIIQRDNGYQPNY SEQ ID NO: 98 TIPRGIEYIQHNGVV SEQ ID NO: 99 GYFAANIDLMMIEEY SEQ ID NO: 100 IPRGIEYIQHNGWQ SEQ ID NO: 101 LDAFRHYDGRTIIQRSEQ ID NO: 102 NKIREALAQTHSAIA SEQ ID NO: 103 RGIEYIQHNGVVQES SEQ ID NO: 104 TNACSINGNAPAEID SEQ ID NO: 105 GYQPNYHAVNIVGYS SEQ ID NO: 106 PRGIEYIQHNGVVQE SEQ ID NO: 107 ESVKYVQSNGGAINH SEQ ID NO: 108 PRGIEYIQHNGVVQE SEQ ID NO: 109 RTIIQRDNGYQPNYH SEQ ID NO: 110 TESAYLAYRNQSLDL SEQ ID NO: 111 ATESAYLAYRNQSLD SEQ ID NO: 112 DLRQMRTVTPIRMQG SEQ ID NO: 113 ESVKYVQSNGGAINH SEQ ID NO: 114 ESVKYVQSNGGAINH SEQ ID NO: 115 TFEEYKKAFNKSYAT SEQ ID NO: 116 YQPNYHAVNIVGYSN SEQ ID NO: 117 DGRTIIQRDNGYQPN SEQ ID NO: 118 FNKSYATFEDEEAAR SEQ ID NO: 119 QGVDYWIVRNSWDTN SEQ ID NO: 120 SVKYVQSNGGAINHL SEQ ID NO: 121 FEEYKKAFNKSYATF SEQ ID NO: 122 TIPRGIEYIQHNGVV SEQ ID NO: 123 DLDAFRHYDGRTIIQ SEQ ID NO: 124 AIAVIIGIKDLDAFR SEQ ID NO: 125 AIAVIIGIKDLDAFR SEQ ID NO: 126 SSIKTFEEYKKAFNK SEQ ID NO: 127 GRTIIQRDNGYQPNY SEQ ID NO: 128 GIEYIQHNGVVQESY SEQ ID NO: 129 QPNYHAVNIVGYSNA SEQ ID NO: 130 NKSYATFEDEEAARK SEQ ID NO: 131 NKSYATFEDEEAARK SEQ ID NO: 132 GDNGYGYFAANIDLM SEQ ID NO: 133 NKSYATFEDEEAARK SEQ ID NO: 134 QPNYHAVNIVGYSNA SEQ ID NO: 135 CSINGNAPAEIDLRQ SEQ ID NO: 136 INHLSDLSLDEFKNR SEQ ID NO: 137 SVKYVQSNGGAINHL SEQ ID NO: 138 IKDLDAFRHYDGRTISEQ ID NO: 139 PRGIEYIQHNGVVQE SEQ ID NO: 140 AVIIGIKDLDAFRHY SEQ ID NO: 141 RGIEYIQHNGVVQES SEQ ID NO: 142 QESYYRYVAREQSCR SEQ ID NO: 143 EYKKAFNKSYATFED SEQ ID NO: 144 PRGIEYIQHNGVVQE SEQ ID NO: 145 APAEIDLRQMRTVTP SEQ ID NO: 146 EALAQTHSAIAVIIG SEQ ID NO: 147 YQPNYHAVNIVGYSN SEQ ID NO: 148 HLKTQFDLNAETNAC SEQ ID NO: 149 EAFEHLKTQFDLNAE SEQ ID NO: 150 NFLESVKYVQSNGGA SEQ ID NO: 151 DNGYGYFAANIDLMM SEQ ID NO: 152 LESVKYVQSNGGAIN SEQ ID NO: 153 YGYFAANIDLMMIEE SEQ ID NO: 154 PSSIKTFEEYKKAFN SEQ ID NO: 155 GIEYIQHNGVVQESY SEQ ID NO: 156 QESYYRYVAREQSCR SEQ ID NO: 157 AATESAYLAYRNQSL SEQ ID NO: 158 KKAFNKSYATFEDEE SEQ ID NO: 159 NGYGYFAANIDLMMI SEQ ID NO: 160 WGDNGYGYFAANIDL SEQ ID NO: 161 LESVKYVQSNGGAIN SEQ ID NO: 162 VVQESYYRYVAREQS SEQ ID NO: 163 ESAYLAYRNQSLDLA SEQ ID NO: 164 LESVKYVQSNGGAIN SEQ ID NO: 165 GVDYWIVRNSWDTNW SEQ ID NO: 166 RQMRTVTPIRMQGGC SEQ ID NO: 167 GYGYFAANIDLMMIE SEQ ID NO: 168 IIGIKDLDAFRHYDG SEQ ID NO: 169 AEAFEHLKTQFDLNA SEQ ID NO: 170 IPRGIEYIQHNGVVQ SEQ ID NO: 171 NIVGYSNAQGVDYWI SEQ ID NO: 172 CWAFSGVAATESAYL SEQ ID NO: 173 PNYHAVNIVGYSNAQ SEQ ID NO: 174 DAFRHYDGRTIIQRD SEQ ID NO: 175 AEAFEHLKTQFDLNASEQ ID NO: 176 IDLRQMRTVTPIRMQ SEQ ID NO: 177 DGRTIIQRDNGYQPN SEQ ID NO: 178 FNKSYATFEDEEAAR SEQ ID NO: 179 FNKSYATFEDEEAAR SEQ ID NO: 180 TFEEYKKAFNKSYAT SEQ ID NO: 181 GYQPNYHAVNIVGYS SEQ ID NO: 182 YQPNYHAVNIVGYSN SEQ ID NO: 183 VVQESYYRYVAREQS SEQ ID NO: 184 ESYYRYVAREQSCRR SEQ ID NO: 185 KTFEEYKKAFNKSYA SEQ ID NO: 186 SNGGAINHLSDLSLD SEQ ID NO: 187 IPRGIEYIQHNGWQ SEQ ID NO: 188 ESAYLAYRNQSLDLA SEQ ID NO: 189 YRYVAREQSCRRPNA SEQ ID NO: 190 IPRGIEYIQHNGWQ SEQ ID NO: 191 AVNIVGYSNAQGVDY SEQ ID NO: 192 DGRTIIQRDNGYQPN SEQ ID NO: 193 VQESYYRYVAREQSC SEQ ID NO: 194 KSYATFEDEEAARKN SEQ ID NO: 195 EYIQHNGVVQESYYR SEQ ID NO: 196 FNKSYATFEDEEAAR SEQ ID NO: 197 FNKSYATFEDEEAAR SEQ ID NO: 198 YYRYVAREQSCRRPN SEQ ID NO: 199 IPRGIEYIQHNGWQ SEQ ID NO: 200 GRTIIQRDNGYQPNY SEQ ID NO: 201 KSYATFEDEEAARKN SEQ ID NO: 202 GIKDLDAFRHYDGRT SEQ ID NO: 203 SAEAFEHLKTQFDLN SEQ ID NO: 204 KAFNKSYATFEDEEA SEQ ID NO: 205 RNSWDTNWGDNGYGY SEQ ID NO: 206 LDAFRHYDGRTIIQR SEQ ID NO: 207 AVIIGIKDLDAFRHY SEQ ID NO: 208 PPNVNKIREALAQTH SEQ ID NO: 209 AQGVDYWIVRNSWDT SEQ ID NO: 210 TIPRGIEYIQHNGW SEQ ID NO: 211 LRQMRTVTPIRMQGG SEQ ID NO: 212 FEEYKKAFNKSYATFSEQ ID NO: 213 ESYYRYVAREQSCRR SEQ ID NO: 214 KDLDAFRHYDGRTII SEQ ID NO: 215 NKSYATFEDEEAARK SEQ ID NO: 216 RGIEYIQHNGVVQES SEQ ID NO: 217 VNKIREALAQTHSAI SEQ ID NO: 218 RPSSIKTFEEYKKAF SEQ ID NO: 219 EEYKKAFNKSYATFE SEQ ID NO: 220 GYQPNYHAVNIVGYS SEQ ID NO: 221 NVNKIREALAQTHSA SEQ ID NO: 222 NFLESVKYVQSNGGA SEQ ID NO: 223 YKKAFNKSYATFEDE SEQ ID NO: 224 NGYGYFAANIDLMMI SEQ ID NO: 225 AINHLSDLSLDEFKN SEQ ID NO: 226 DGRTIIQRDNGYQPN SEQ ID NO: 227 TIIQRDNGYQPNYHA SEQ ID NO: 228 HAVNIVGYSNAQGVD SEQ ID NO: 229 KSYATFEDEEAARKN SEQ ID NO: 230 VIIGIKDLDAFRHYD SEQ ID NO: 231 GYQPNYHAVNIVGYS SEQ ID NO: 232 LRQMRTVTPIRMQGG SEQ ID NO: 233 SAEAFEHLKTQFDLN SEQ ID NO: 234 VQESYYRYVAREQSC SEQ ID NO: 235 RGIEYIQHNGVVQES SEQ ID NO: 236 SINGNAPAEIDLRQM SEQ ID NO: 237 VRNSWDTNWGDNGYG SEQ ID NO: 238 FLESVKYVQSNGGAI SEQ ID NO: 239 TESAYLAYRNQSLDL SEQ ID NO: 240 KTFEEYKKAFNKSYA SEQ ID NO: 241 PNYHAVNIVGYSNAQ SEQ ID NO: 242 TIIQRDNGYQPNYHA SEQ ID NO: 243 TIPRGIEYIQHNGVV SEQ ID NO: 244 GAINHLSDLSLDEFK SEQ ID NO: 245 KYVQSNGGAINHLSD SEQ ID NO: 246 AFNKSYATFEDEEAA SEQ ID NO: 247 AEAFEHLKTQFDLNA SEQ ID NO: 248 AYLAYRNQSLDLAEQ SEQ ID NO: 249 NGYQPNYHAVNIVGYSEQ ID NO: 250 YHAVNIVGYSNAQGV SEQ ID NO: 251 QESYYRYVAREQSCR SEQ ID NO: 252 AFNKSYATFEDEEAA SEQ ID NO: 253 FSGVAATESAYLAYR SEQ ID NO: 254 GYFAANIDLMMIEEY SEQ ID NO: 255 EYKKAFNKSYATFED SEQ ID NO: 256 VIIGIKDLDAFRHYD SEQ ID NO: 257 DAFRHYDGRTIIQRD SEQ ID NO: 258 HSAIAVIIGIKDLDA SEQ ID NO: 259 YDGRTIIQRDNGYQP SEQ ID NO: 260 ATESAYLAYRNQSLD SEQ ID NO: 261 SYYRYVAREQSCRRP SEQ ID NO: 262 SYATFEDEEAARKNF SEQ ID NO: 263 AFRHYDGRTIIQRDN SEQ ID NO: 264 AFNKSYATFEDEEAA SEQ ID NO: 265 VNIVGYSNAQGVDYW SEQ ID NO: 266 YRYVAREQSCRRPNA SEQ ID NO: 267 INGNAPAEIDLRQMR SEQ ID NO: 268 DTIPRGIEYIQHNGV SEQ ID NO: 269 EHLKTQFDLNAETNA SEQ ID NO: 270 GRTIIQRDNGYQPNY SEQ ID NO: 271 KNRFLMSAEAFEHLK SEQ ID NO: 272 PNYHAVNIVGYSNAQ SEQ ID NO: 273 QGVDYWIVRNSWDTN SEQ ID NO: 274 IIGIKDLDAFRHYDG SEQ ID NO: 275 GIEYIQHNGWQESY SEQ ID NO: 276 SAYLAYRNQSLDLAE SEQ ID NO: 277 NWGDNGYGYFAANID SEQ ID NO: 278 ACSINGNAPAEIDLR SEQ ID NO: 279 VKYVQSNGGAINHLS SEQ ID NO: 280 DNGYGYFAANIDLMM SEQ ID NO: 281 AVNIVGYSNAQGVDY SEQ ID NO: 282 YPPNVNKIREALAQT SEQ ID NO: 283 KSYATFEDEEAARKNSEQ ID NO: 682 TNACSINGNAP SEQ ID NO: 683 TNACSINGNAPASEQ ID NO: 684 APAEIDLRQMRTSEQ ID NO: 685 EIDLRQMRTVTPSEQ ID NO: 686 EIDLRQMRTVTPISEQ ID NO: 687 LRQMRTVTPIRMSEQ ID NO: 688 MRTVTPIRMQGGSEQ ID NO: 689 VTPIRMQGGCSEQ ID NO: 690 QGGCGSCWAFSGSEQ ID NO: 691 QGGCGSCWAFSGVAATES SEQ ID NO: 692 CWAFSGVAATESSEQ ID NO: 693 VAATESAYLAYRSEQ ID NO: 694 NQSLDLAEQELVDCASEQ ID NO: 695 NQSLDLAEQELVDCASEQ ID NO: 696 GIEYIQHNGWQESYSEQ ID NO: 697 YIQHNGVVQESYSEQ ID NO: 698 HNGVVQESYYRYSEQ ID NO: 699 HNGVVQESYYRYVARSEQ ID NO: 700 VVQESYYRYVARSEQ ID NO: 701 ESYYRYVAREQSSEQ ID NO: 702 PNAQRFGISNYCQIYPPN SEQ ID NO: 703 QRFGISNYCQIYPPNSEQ ID NO: 704 NYCQIYPPNVNKSEQ ID NO: 705 PNVNKIREALAQTHSEQ ID NO: 706 VNKIREALAQTHSAIASEQ ID NO: 707 ALAQTHSAIAVIIGIKSEQ ID NO: 708 AVIIGIKDLDAFSEQ ID NO: 709 KDLDAFRHYDGRSEQ ID NO: 710 KDLDAFRHYDGRTIISEQ ID NO: 711 DAFRHYDGRTIIQSEQ ID NO: 712 RHYDGRTIIQRDNGYQPN SEQ ID NO: 713 RHYDGRTIIQRDSEQ ID NO: 714 TIIQRDNGYQPNSEQ ID NO: 715 NGYQPNYHAVNISEQ ID NO: 716 QPNYHAVNIVGYSNAQGVDYW SEQ ID NO: 717 YHAVNIVGYSNAQGVSEQ ID NO: 718 VNIVGYSNAQGVSEQ ID NO: 719 VNIVGYSNAQGVDYWSEQ ID NO: 720 VNIVGYSNAQGVDSEQ ID NO: 721 VGYSNAQGVDYWIVRSEQ ID NO: 722 NGYGYFAANIDLMSEQ ID NO: 723 DLMMIEEYPYViii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) sequence identity to Der f 1 house dust mite polypeptide (e.g., Der f 1 Isoform 0101), preferably selected from the group consisting of: (a”)-(c”), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a”) SEQ ID NO: 284 (TSACRINSVNVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAA TESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQN GWEERSYPYVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREA LTQTHTAIAVIIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVG YGSTQGVDYWI VRNSWDTTWG DSGYGYFQAGN N LMM I EQYPY VVIM);b”) SEQ ID NO: 285 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAE); and c”) SEQ ID NO: 286 (RPASIKTFEEFKKAFNKNYATVEEEEVARKNFLESLKYVEANKG AINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAETSACRINSV NVPSELDLRSLRTVTPIRMQGGCGSCWAFSGVAATESAYLAYR NTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQQNGWEERSYP YVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREALTQTHTAIAV IIGIKDLRAFQHYDGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDYWl VR N SWDTTWG DSG YG YFQAG N N LM M I EQYPYVVI M) ;iv) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 1 -derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1 -derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 287 AVNIVGYGSTQGVDY SEQ ID NO: 288 HAVNIVGYGSTQGVD SEQ ID NO: 289 VNIVGYGSTQGVDYW SEQ ID NO: 290 YHAVNIVGYGSTQGV SEQ ID NO: 291 FSGVAATESAYLAYR SEQ ID NO: 292 DNGYQPNYHAVNIVG SEQ ID NO: 293 HDNGYQPNYHAVNIV SEQ ID NO: 294 PRGIEYIQQNGVVEE SEQ ID NO: 295 PRGIEYIQQNGVVEE SEQ ID NO: 296 AFSGVAATESAYLAY SEQ ID NO: 297 QHDNGYQPNYHAVNI SEQ ID NO: 298 ESAYLAYRNTSLDLS SEQ ID NO: 299 IPRGIEYIQQNGWE SEQ ID NO: 300 IPRGIEYIQQNGWE SEQ ID NO: 301 WAFSGVAATESAYLA SEQ ID NO: 302 SGVAATESAYLAYRN SEQ ID NO: 303 TESAYLAYRNTSLDL SEQ ID NO: 304 NGYQPNYHAVNIVGY SEQ ID NO: 305 LRAFQHYDGRTIIQH SEQ ID NO: 306 ATESAYLAYRNTSLD SEQ ID NO: 307 GRTIIQHDNGYQPNY SEQ ID NO: 308 DLRAFQHYDGRTIIQ SEQ ID NO: 309 IAVIIGIKDLRAFQH SEQ ID NO: 310 YLAYRNTSLDLSEQE SEQ ID NO: 311 TIPRGIEYIQQNGVV SEQ ID NO: 312 QPNYHAVNIVGYGST SEQ ID NO: 313 GIEYIQQNGWEERS SEQ ID NO: 314 RAFQHYDGRTIIQHD SEQ ID NO: 315 DGRTIIQHDNGYQPN SEQ ID NO: 316 IKDLRAFQHYDGRTI SEQ ID NO: 317 GIKDLRAFQHYDGRT SEQ ID NO: 318 RGIEYIQQNGWEER SEQ ID NO: 319 TIPRGIEYIQQNGVV SEQ ID NO: 320 KDLRAFQHYDGRTII SEQ ID NO: 321 YQPNYHAVNIVGYGS SEQ ID NO: 322 IEYIQQNGVVEERSY SEQ ID NO: 323 AIAVIIGIKDLRAFQSEQ ID NO: 324 NIVGYGSTQGVDYWI SEQ ID NO: 325 RTIIQHDNGYQPNYH SEQ ID NO: 326 PRGIEYIQQNGVVEE SEQ ID NO: 327 LRSLRTVTPIRMQGG SEQ ID NO: 328 IAVIIGIKDLRAFQH SEQ ID NO: 329 SAYLAYRNTSLDLSE SEQ ID NO: 330 RGIEYIQQNGVVEER SEQ ID NO: 331 GRTIIQHDNGYQPNY SEQ ID NO: 332 AYLAYRNTSLDLSEQ SEQ ID NO: 333 QPNYHAVNIVGYGST SEQ ID NO: 334 IQHDNGYQPNYHAVN SEQ ID NO: 335 RGIEYIQQNGVVEER SEQ ID NO: 336 GYQPNYHAVNIVGYG SEQ ID NO: 337 QNGVVEERSYPYVAR SEQ ID NO: 338 QNGVVEERSYPYVAR SEQ ID NO: 339 NYHAVNIVGYGSTQG SEQ ID NO: 340 IREALTQTHTAIAVI SEQ ID NO: 341 DLRSLRTVTPIRMQG SEQ ID NO: 342 LAYRNTSLDLSEQEL SEQ ID NO: 343 QNGVVEERSYPYVAR SEQ ID NO: 344 DGRTIIQHDNGYQPN SEQ ID NO: 345 IGIKDLRAFQHYDGR SEQ ID NO: 346 AIAVIIGIKDLRAFQ SEQ ID NO: 347 REALTQTHTAIAVII SEQ ID NO: 348 DGRTIIQHDNGYQPN SEQ ID NO: 349 AVIIGIKDLRAFQHY SEQ ID NO: 350 LRAFQHYDGRTIIQH SEQ ID NO: 351 AIAVIIGIKDLRAFQ SEQ ID NO: 352 YQPNYHAVNIVGYGS SEQ ID NO: 353 QQNGVVEERSYPYVA SEQ ID NO: 354 QNGVVEERSYPYVAR SEQ ID NO: 355 QIREALTQTHTAIAV SEQ ID NO: 356 YDGRTIIQHDNGYQP SEQ ID NO: 357 IPRGIEYIQQNGVVE SEQ ID NO: 358 ESAYLAYRNTSLDLS SEQ ID NO: 359 RTIIQHDNGYQPNYH SEQ ID NO: 360 GYGYFQAGNNLMMIESEQ ID NO: 361 DLRAFQHYDGRTIIQ SEQ ID NO: 362 PRGIEYIQQNGVVEE SEQ ID NO: 363 RTIIQHDNGYQPNYH SEQ ID NO: 364 TAIAVIIGIKDLRAF SEQ ID NO: 365 GYGYFQAGNNLMMIE SEQ ID NO: 366 QPNYHAVNIVGYGST SEQ ID NO: 367 QGVDYWIVRNSWDTT SEQ ID NO: 368 GRTIIQHDNGYQPNY SEQ ID NO: 369 PRGIEYIQQNGVVEE SEQ ID NO: 370 YQPNYHAVNIVGYGS SEQ ID NO: 371 GIEYIQQNGVVEERS SEQ ID NO: 372 RSLRTVTPIRMQGGC SEQ ID NO: 373 GRTIIQHDNGYQPNY SEQ ID NO: 374 QQNGVVEERSYPYVA SEQ ID NO: 375 QQNGVVEERSYPYVA SEQ ID NO: 376 TESAYLAYRNTSLDL SEQ ID NO: 377 ATESAYLAYRNTSLD SEQ ID NO: 378 TAIAVIIGIKDLRAF SEQ ID NO: 379 QPNYHAVNIVGYGST SEQ ID NO: 380 HTAIAVIIGIKDLRA SEQ ID NO: 381 DTIPRGIEYIQQNGV SEQ ID NO: 382 YDGRTIIQHDNGYQP SEQ ID NO: 383 QQNGVVEERSYPYVA SEQ ID NO: 384 LDLRSLRTVTPIRMQ SEQ ID NO: 385 CWAFSGVAATESAYL SEQ ID NO: 386 IQQNGVVEERSYPYV SEQ ID NO: 387 EYIQQNGVVEERSYP SEQ ID NO: 388 PRGIEYIQQNGVVEE SEQ ID NO: 389 GYQPNYHAVNIVGYG SEQ ID NO: 390 LRSLRTVTPIRMQGG SEQ ID NO: 391 IIGIKDLRAFQHYDG SEQ ID NO: 392 RGIEYIQQNGVVEER SEQ ID NO: 393 AVIIGIKDLRAFQHY SEQ ID NO: 394 SAYLAYRNTSLDLSE SEQ ID NO: 395 PNYHAVNIVGYGSTQ SEQ ID NO: 396 GVDYWIVRNSWDTTW SEQ ID NO: 397 IPRGIEYIQQNGVVESEQ ID NO: 398 YQPNYHAVNIVGYGS SEQ ID NO: 399 IAVIIGIKDLRAFQH SEQ ID NO: 400 RAFQHYDGRTIIQHD SEQ ID NO: 401 SGYGYFQAGNNLMMI SEQ ID NO: 402 DVKQIREALTQTHTA SEQ ID NO: 403 VKQIREALTQTHTAI SEQ ID NO: 404 NVPSELDLRSLRTVT SEQ ID NO: 405 IVGYGSTQGVDYWIV SEQ ID NO: 406 GYQPNYHAVNIVGYG SEQ ID NO: 407 DGRTIIQHDNGYQPN SEQ ID NO: 408 TIIQHDNGYQPNYHA SEQ ID NO: 409 SGYGYFQAGNNLMMI SEQ ID NO: 410 TQGVDYWIVRNSWDT SEQ ID NO: 411 NIVGYGSTQGVDYWI SEQ ID NO: 412 SYPYVAREQQCRRPN SEQ ID NO: 413 GYQPNYHAVNIVGYG SEQ ID NO: 414 DSGYGYFQAGNNLMM SEQ ID NO: 415 IPRGIEYIQQNGVVE SEQ ID NO: 416 LRSLRTVTPIRMQGG SEQ ID NO: 417 VNVPSELDLRSLRTV SEQ ID NO: 418 GYGYFQAGNNLMMIE SEQ ID NO: 419 PPDVKQIREALTQTH SEQ ID NO: 420 KDLRAFQHYDGRTII SEQ ID NO: 421 IQQNGVVEERSYPYV SEQ ID NO: 422 YGYFQAGNNLMMIEQ SEQ ID NO: 423 AATESAYLAYRNTSL SEQ ID NO: 424 IIGIKDLRAFQHYDG SEQ ID NO: 425 HTAIAVIIGIKDLRA SEQ ID NO: 426 NGVVEERSYPYVARE SEQ ID NO: 427 TAIAVIIGIKDLRAF SEQ ID NO: 428 VNIVGYGSTQGVDYW SEQ ID NO: 429 NGYQPNYHAVNIVGY SEQ ID NO: 430 RGIEYIQQNGVVEER SEQ ID NO: 431 PRGIEYIQQNGVVEE SEQ ID NO: 432 VIIGIKDLRAFQHYD SEQ ID NO: 433 FSGVAATESAYLAYR SEQ ID NO: 434 RGIEYIQQNGVVEERSEQ ID NO: 435 GIKDLRAFQHYDGRTSEQ ID NO: 436 DLRSLRTVTPIRMQGSEQ ID NO: 437 NGVVEERSYPYVARESEQ ID NO: 438 YPYVAREQQCRRPNSSEQ ID NO: 439 IKDLRAFQHYDGRTISEQ ID NO: 440 RAFQHYDGRTIIQHDSEQ ID NO: 441 YDGRTIIQHDNGYQPSEQ ID NO: 442 IAVIIGIKDLRAFQHSEQ ID NO: 443 KQIREALTQTHTAIASEQ ID NO: 444 IAVIIGIKDLRAFQHSEQ ID NO: 445 TIPRGIEYIQQNGVVSEQ ID NO: 446 DSGYGYFQAGNNLMMSEQ ID NO: 447 RSYPYVAREQQCRRPSEQ ID NO: 448 PNYHAVNIVGYGSTQv) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 2 house dust mite polypeptide (e.g., Der p 2 Isoform 0110), preferably selected from the group consisting of: (a’”), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a’”) SEQ ID NO: 449 (DQVDVKDCANHEIKKVLVPGCHGSEPCIIHRGKPFQLEAVFEAN QNSKTAKI El KASI DGLEVDVPGI DPNACHYM KCPLVKGQQYDI K YTWNVPKIAPKSENVWTVKVMGDNGVLACAIATHAKIRD); vi) a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 2-derived HLA-binding peptides (e.g., as in Table 2 and / or 3 herein), preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA- binding peptides selected from the group consisting of:SEQ ID NO: 450 LEAVFEANQNSKTAKSEQ ID NO: 451 EAVFEANQNSKTAKISEQ ID NO: 452 QLEAVFEANQNSKTASEQ ID NO: 453 DIKYTWNVPKIAPKS SEQ ID NO: 454 YDIKYTWNVPKIAPK SEQ ID NO: 455 AVFEANQNSKTAKIE SEQ ID NO: 456 QYDIKYTWNVPKIAP SEQ ID NO: 457 IKYTWNVPKIAPKSE SEQ ID NO: 458 KASIDGLEVDVPGID SEQ ID NO: 459 FQLEAVFEANQNSKT SEQ ID NO: 460 QYDIKYTWNVPKIAP SEQ ID NO: 461 VFEANQNSKTAKIEI SEQ ID NO: 462 IKASIDGLEVDVPGI SEQ ID NO: 463 IDGLEVDVPGIDPNA SEQ ID NO: 464 KYTWNVPKIAPKSEN SEQ ID NO: 465 QQYDIKYTWNVPKIA SEQ ID NO: 466 SIDGLEVDVPGIDPN SEQ ID NO: 467 QQYDIKYTWNVPKIA SEQ ID NO: 468 YDIKYTWNVPKIAPK SEQ ID NO: 469 IDGLEVDVPGIDPNA SEQ ID NO: 470 GKPFQLEAVFEANQN SEQ ID NO: 471 EIKASIDGLEVDVPG SEQ ID NO: 472 GKPFQLEAVFEANQN SEQ ID NO: 473 VVVTVKVMGDNGVLA SEQ ID NO: 474 ASIDGLEVDVPGIDP SEQ ID NO: 475 DGLEVDVPGIDPNAC SEQ ID NO: 476 SIDGLEVDVPGIDPN SEQ ID NO: 477 GQQYDIKYTWNVPKI SEQ ID NO: 478 GKPFQLEAVFEANQN SEQ ID NO: 479 DIKYTWNVPKIAPKS SEQ ID NO: 480 LEAVFEANQNSKTAK SEQ ID NO: 481 RGKPFQLEAVFEANQ SEQ ID NO: 482 EAVFEANQNSKTAKI SEQ ID NO: 483 PKSENVVVTVKVMGD SEQ ID NO: 484 ASIDGLEVDVPGIDP SEQ ID NO: 485 VPKIAPKSENVVVTV SEQ ID NO: 486 LEAVFEANQNSKTAK SEQ ID NO: 487 DGLEVDVPGIDPNAC SEQ ID NO: 488 VTVKVMGDNGVLACA SEQ ID NO: 489 TAKIEIKASIDGLEVSEQ ID NO: 490 VTVKVMGDNGVLACA SEQ ID NO: 491 TVKVMGDNGVLACAI SEQ ID NO: 492 TVKVMGDNGVLACAI SEQ ID NO: 493 NVPKIAPKSENVVVT SEQ ID NO: 494 RGKPFQLEAVFEANQ SEQ ID NO: 495 RGKPFQLEAVFEANQ SEQ ID NO: 496 EAVFEANQNSKTAKI SEQ ID NO: 497 GKPFQLEAVFEANQN SEQ ID NO: 498 QYDIKYTWNVPKIAP SEQ ID NO: 499 ASIDGLEVDVPGIDP SEQ ID NO: 500 SENVVVTVKVMGDNG SEQ ID NO: 501 KTAKIEIKASIDGLE SEQ ID NO: 502 VPGIDPNACHYMKCP SEQ ID NO: 503 APKSENVVVTVKVMG SEQ ID NO: 504 DIKYTWNVPKIAPKS SEQ ID NO: 505 VVTVKVMGDNGVLAC SEQ ID NO: 506 QLEAVFEANQNSKTA SEQ ID NO: 507 GQQYDIKYTWNVPKI SEQ ID NO: 508 YDIKYTWNVPKIAPK SEQ ID NO: 509 KGQQYDIKYTWNVPK SEQ ID NO: 510 QYDIKYTWNVPKIAP SEQ ID NO: 511 DIKYTWNVPKIAPKS SEQ ID NO: 512 VDVPGIDPNACHYMK SEQ ID NO: 513 KSENVVVTVKVMGDN SEQ ID NO: 514 RGKPFQLEAVFEANQ SEQ ID NO: 515 KGQQYDIKYTWNVPK SEQ ID NO: 516 VVTVKVMGDNGVLAC SEQ ID NO: 517 YDIKYTWNVPKIAPK SEQ ID NO: 518 NVVVTVKVMGDNGVL SEQ ID NO: 519 VVVTVKVMGDNGVLA SEQ ID NO: 520 IDGLEVDVPGIDPNA SEQ ID NO: 521 QQYDIKYTWNVPKIA SEQ ID NO: 522 IKYTWNVPKIAPKSE SEQ ID NO: 523 VVTVKVMGDNGVLAC SEQ ID NO: 524 WNVPKIAPKSENVVV SEQ ID NO: 525 KASIDGLEVDVPGID SEQ ID NO: 526 GKPFQLEAVFEANQNSEQ ID NO: 527 IAPKSENVVVTVKVMSEQ ID NO: 528 KSENVVVTVKVMGDNSEQ ID NO: 529 KPFQLEAVFEANQNSSEQ ID NO: 530 SENVVVTVKVMGDNGSEQ ID NO: 531 PKIAPKSENVVVTVKSEQ ID NO: 532 GQQYDIKYTWNVPKISEQ ID NO: 533 QQYDIKYTWNVPKIASEQ ID NO: 534 DVPGIDPNACHYMKCSEQ ID NO: 724 DQVDVKDCANHEIKKSEQ ID NO: 725 HGSEPCIIHRGKSEQ ID NO: 726 HGSEPCIIHRGKSEQ ID NO: 727 HGSEPCIIHRGKPFQSEQ ID NO: 728 HGSEPCIIHRGKPFQLEASEQ ID NO: 729 EPCIIHRGKPFQLEASEQ ID NO: 730 EPCIIHRGKPFQLEALFESEQ ID NO: 731 LEALFEANQNTKNAKSEQ ID NO: 732 LEALFEANQNTKNAKSEQ ID NO: 733 LEALFEANQNTKNAKSEQ ID NO: 734 LEALFEANQNTKNAKIEIKASIDG (+49-60Epitop corresponding to SEQ ID NO: 748) SEQ ID NO: 735 LFEANQNTKNAKSEQ ID NO: 736 NTKNAKIEIKASSEQ ID NO: 737 DVPGIDPNACHYVKCPLVKGQSEQ ID NO: 738 GIDPNACHYVKCPLVSEQ ID NO: 739 PNACHYVKCPLVKGQSEQ ID NO: 740 QYDIKYTWNVPKIAPSEQ ID NO: 741 VPKIAPKSENVVSEQ ID NO: 742 VPKIAPKSENVVVTVKVLSEQ ID NO: 743 GVLACAIATHAKvii) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 2 house dust mite polypeptide (e.g., Der f 2 Isoform 0102), preferably selected from the group consisting of: (a””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a””) SEQ ID NO: 535 (DQVDVKDCANNEIKKVMVDGCHGSDPCIIHRGKPFTLEALFDAN QNTKTAKI El KASLDGLEI DVPGI DTNACH FM KCPLVKGQQYDI KY TWNVPKIAPKSENVVVTVKLIGDNGVLACAIATHGKIRD); viii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 2-derived H LA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived H LA-binding peptides selected from the group consisting of:SEQ ID NO: 536 LEALFDANQNTKTAKSEQ ID NO: 537 EALFDANQNTKTAKISEQ ID NO: 538 DIKYTWNVPKIAPKSSEQ ID NO: 539 YDIKYTWNVPKIAPKSEQ ID NO: 540 TLEALFDANQNTKTASEQ ID NO: 541 QYDIKYTWNVPKIAPSEQ ID NO: 542 ALFDANQNTKTAKIESEQ ID NO: 543 IKYTWNVPKIAPKSESEQ ID NO: 544 NNEIKKVMVDGCHGSSEQ ID NO: 545 ANNEIKKVMVDGCHGSEQ ID NO: 546 QYDIKYTWNVPKIAPSEQ ID NO: 547 KASLDGLEI DVPGI DSEQ ID NO: 548 KYTWNVPKIAPKSENSEQ ID NO: 549 QQYDIKYTWNVPKIASEQ ID NO: 550 QQYDIKYTWNVPKIASEQ ID NO: 551 CANNEIKKVMVDGCHSEQ ID NO: 552 VTVKLIGDNGVLACASEQ ID NO: 553 LDGLEIDVPGIDTNASEQ ID NO: 554 NEIKKVMVDGCHGSDSEQ ID NO: 555 YDIKYTWNVPKIAPKSEQ ID NO: 556 FTLEALFDANQNTKTSEQ ID NO: 557 TVKLIGDNGVLACAISEQ ID NO: 558 SLDGLEIDVPGIDTNSEQ ID NO: 559 LDGLEIDVPGIDTNASEQ ID NO: 560 TVKLIGDNGVLACAI SEQ ID NO: 561 VTVKLIGDNGVLACA SEQ ID NO: 562 IKASLDGLEIDVPGI SEQ ID NO: 563 LFDANQNTKTAKIEI SEQ ID NO: 564 VVTVKLIGDNGVLAC SEQ ID NO: 565 GQQYDIKYTWNVPKI SEQ ID NO: 566 DGLEIDVPGIDTNAC SEQ ID NO: 567 SLDGLEIDVPGIDTN SEQ ID NO: 568 DIKYTWNVPKIAPKS SEQ ID NO: 569 VWTVKLIGDNGVLA SEQ ID NO: 570 ASLDGLEIDVPGIDT SEQ ID NO: 571 VPKIAPKSENVVVTV SEQ ID NO: 572 PKSENVVVTVKLIGD SEQ ID NO: 573 NVPKIAPKSENVVVT SEQ ID NO: 574 DGLEIDVPGIDTNAC SEQ ID NO: 575 TVKLIGDNGVLACAI SEQ ID NO: 576 VVTVKLIGDNGVLAC SEQ ID NO: 577 VWTVKLIGDNGVLA SEQ ID NO: 578 EIKASLDGLEIDVPG SEQ ID NO: 579 EIKKVMVDGCHGSDP SEQ ID NO: 580 SENVVVTVKLIGDNG SEQ ID NO: 581 QYDIKYTWNVPKIAP SEQ ID NO: 582 GKPFTLEALFDANQN SEQ ID NO: 583 VTVKLIGDNGVLACA SEQ ID NO: 584 VKLIGDNGVLACAIA SEQ ID NO: 585 TAKIEIKASLDGLEI SEQ ID NO: 586 KSENVVVTVKLIGDN SEQ ID NO: 587 DIKYTWNVPKIAPKS SEQ ID NO: 588 KTAKIEIKASLDGLE SEQ ID NO: 589 VKLIGDNGVLACAIA SEQ ID NO: 590 GQQYDIKYTWNVPKI SEQ ID NO: 591 YDIKYTWNVPKIAPK SEQ ID NO: 592 KGQQYDIKYTWNVPK SEQ ID NO: 593 QYDIKYTWNVPKIAP SEQ ID NO: 594 DIKYTWNVPKIAPKS SEQ ID NO: 595 ASLDGLEIDVPGIDT SEQ ID NO: 596 LEALFDANQNTKTAKSEQ ID NO: 597 EALFDANQNTKTAKISEQ ID NO: 598 SENVVVTVKLIGDNGSEQ ID NO: 599 APKSENVVVTVKLIGSEQ ID NO: 600 KGQQYDIKYTWNVPKSEQ ID NO: 601 EIKKVMVDGCHGSDPSEQ ID NO: 602 YDIKYTWNVPKIAPKSEQ ID NO: 603 QQYDIKYTWNVPKIASEQ ID NO: 604 RGKPFTLEALFDANQSEQ ID NO: 605 IKYTWNVPKIAPKSESEQ ID NO: 606 WNVPKIAPKSENVVVSEQ ID NO: 607 ASLDGLEIDVPGIDTSEQ ID NO: 608 LEALFDANQNTKTAKSEQ ID NO: 609 VVVTVKLIGDNGVLASEQ ID NO: 610 KSENVVVTVKLIGDNSEQ ID NO: 611 IKKVMVDGCHGSDPCSEQ ID NO: 612 PKIAPKSENVVVTVKSEQ ID NO: 613 KASLDGLEIDVPGIDSEQ ID NO: 614 VKLIGDNGVLACAIASEQ ID NO: 615 ENVVVTVKLIGDNGVSEQ ID NO: 616 GQQYDIKYTWNVPKISEQ ID NO: 617 QQYDIKYTWNVPKIASEQ ID NO: 618 ENVVVTVKLIGDNGVSEQ ID NO: 619 NEIKKVMVDGCHGSDSEQ ID NO: 620 PKSENVVVTVKLIGDix) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 97%, at least 98%, at least 99% or 100%) %) sequence identity to Der p 23 house dust mite polypeptide (e.g., Der p 23 Isoform 0101), preferably selected from the group consisting of: (a’””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA- DRB5*01:01:a’””) SEQ ID NO: 621 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT);x)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der p 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 622 SRFGYFADPKDPHKFSEQ ID NO: 623 RFGYFADPKDPHKFYSEQ ID NO: 624 PSRFGYFADPKDPHKSEQ ID NO: 625 RFGYFADPKDPHKFYSEQ ID NO: 626 SRFGYFADPKDPHKFSEQ ID NO: 627 PSRFGYFADPKDPHKSEQ ID NO: 628 PHKFYICSNWEAVHKSEQ ID NO: 629 FGYFADPKDPHKFYISEQ ID NO: 630 FGYFADPKDPHKFYISEQ ID NO: 631 PHKFYICSNWEAVHKSEQ ID NO: 632 CPSRFGYFADPKDPHSEQ ID NO: 633 RFGYFADPKDPHKFYSEQ ID NO: 634 PSRFGYFADPKDPHKSEQ ID NO: 635 SRFGYFADPKDPHKFSEQ ID NO: 636 DPHKFYICSNWEAVHSEQ ID NO: 637 CPSRFGYFADPKDPHSEQ ID NO: 638 DPHKFYICSNWEAVHSEQ ID NO: 639 PSRFGYFADPKDPHKSEQ ID NO: 640 HKFYICSNWEAVHKDSEQ ID NO: 641 PSRFGYFADPKDPHKSEQ ID NO: 642 PSRFGYFADPKDPHKSEQ ID NO: 643 GYFADPKDPHKFYICSEQ ID NO: 644 GYFADPKDPHKFYICSEQ ID NO: 645 PHKFYICSNWEAVHKSEQ ID NO: 646 PHKFYICSNWEAVHKSEQ ID NO: 647 I I I VHPTTTEQPDDKxi) a polypeptide having at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100%) %) sequence identity to Der f 23 house dust mite polypeptide (e.g., Der f 23 Isoform 0201), preferablyselected from the group consisting of: (a”””), further preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01:a”””) SEQ ID NO: 648 (ANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFADPKDPHKFY ICSNWEAVHKDCPGNTRWNEDEETCT);SEQ ID NO: 744 (DIDHDDDPTTMIDVQTTTVQPSDEFECPT RFGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT); xii)a polypeptide comprising or consisting of one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) Der f 23-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of:SEQ ID NO: 649 TTMIDVQ I I I VQPSDSEQ ID NO: 650 PTTMIDVQ I I I VORSSEQ ID NO: 651 TMIDVQI I I VQPSDESEQ ID NO: 652 DPTTMIDVQ I I I VQPSEQ ID NO: 653 RFGYFADPKDPCKFYSEQ ID NO: 654 TRFGYFADPKDPCKFSEQ ID NO: 655 PTRFGYFADPKDPCKSEQ ID NO: 656 MIDVQ I I I VQPSDEFSEQ ID NO: 657 RFGYFADPKDPCKFYSEQ ID NO: 658 TRFGYFADPKDPCKFSEQ ID NO: 659 FGYFADPKDPCKFYISEQ ID NO: 660 PTRFGYFADPKDPCKSEQ ID NO: 661 PTTMIDVQ I I I VORSSEQ ID NO: 662 RFGYFADPKDPCKFYSEQ ID NO: 663 DPTTMIDVQ I I I VQPSEQ ID NO: 664 CPTRFGYFADPKDPCSEQ ID NO: 665 TRFGYFADPKDPCKFSEQ ID NO: 666 PTRFGYFADPKDPCKSEQ ID NO: 667 IDVQTTTVQPSDEFESEQ ID NO: 668 FGYFADPKDPCKFYISEQ ID NO: 669 TMIDVQI I I VQPSDESEQ ID NO: 670 DDPTTMIDVQI I I VQSEQ ID NO: 671 PCKFYICSNWEAIHKSEQ ID NO: 672 MIDVQ I I I VQPSDEFThe method of any one of the preceding items, wherein the nucleic acid and / or the polypeptide of any one of preceding items is administered at a dose of about 75 mg to about 600 mg.The method of any one of the preceding items, wherein the nucleic acid and / or the polypeptide of any one of preceding items is administered at a dose of about 300 mg. The method of any one of the preceding items, wherein the initial dose comprises about 600 mg and each secondary dose comprises about 300 mg of the nucleic acid and / or the polypeptide of any one of preceding items, wherein each secondary dose is administered one week or two weeks after the immediately preceding dose.The method of any one of the preceding items, wherein said method further comprising administration of a desensitization or hypo-sensitization agent, preferably said agent comprising faeces and / or dead bodies of dust mites.The method of any one of the preceding items, wherein the dust mites are arthropods belonging to the family Pyroglyphidae, further preferably said dust mites are selected from the group consisting of: Dermatophagoides pteronyssinus, Dermatophagoides farina and Dermatophagoides microceras.A method of producing of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding items; said method comprising: providing one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the nucleic acid constructs of any one of the preceding items, optionally further comprising expressing or translating said one or more the nucleic acid constructs.The method of any one of the preceding items, wherein said method is an in vitro, ex vivo or in vivo method.The nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding items for use as a medicament and / or in therapy. The nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes, and / or composition of any one of the preceding items for use in one or more of the following methods:a) method for treatment, amelioration and / or prophylaxis of allergy, preferably dust mites allergy;b) method for increasing tolerance to dust mites;c) method for reducing a serum allergen-specific IgE level in a subject;d) any method according to any one of the preceding items;e) method of production of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding items;f) any combination of methods as in (a)-(e); and / org) any method according to (a)-(f), wherein said method is an in vitro, in vivo or ex vivo method.49. Use of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding items for / in one or more of the following:a) treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy; b) increasing tolerance to dust mites;c) reducing a serum allergen-specific IgE level in a subject;d) any use according to any one of the preceding items and / or manufacture of a medicament for any use according to any one of the preceding items;e) production of the nucleic acid construct, polypeptide, cell, plurality of cells, LNPs, polymersomes and / or composition of any one of the preceding items; f) any combination of uses as in (a)-(e); and / org) any use according to (a)-(f), wherein said use is an in vitro, in vivo or ex vivo use.50. The nucleic acid construct, polypeptide, cell, plurality of cells, LPNs, polymersomes, composition, method and / or use of any one of the preceding items, carried out as depicted in any of the examples 1-4 section below (e.g., as shown in any one of Figures 1-14 and / or Tables 1-3 herein).51. The nucleic acid construct, polypeptide, cell, plurality of cells, LPNs, polymersomes, composition, method and / or use of any one of the preceding items, capable of promoting a Type-1 immune response (e.g., IFN-mediated), which counteracts the allergic Type-2 response.

[0150] The invention is further characterized by the following embodiments:1. A nucleic acid construct, preferably a RNA construct, comprising or consisting of the following sequences (a), (b), (d) and optionally (c), wherein said sequences are in-frame, preferably in the following order, wherein:a) a nucleic acid sequence encoding for a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1 (e.g., having a Uniprot accession number: Q8VH34), further preferably the polypeptide fragment is at least 15 amino acids long, even further preferably the signal polypeptide has at least 75%sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, most preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2;b) a nucleic acid sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides, preferably allergens, wherein said polypeptides are selected from the group consisting of (i)-(xii) :i) a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of: (a’)-(c’), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA- DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01;a ) SEQ ID NO: 5;b ) SEQ ID NO: 4; andc) SEQ ID NO: 3;ii) a polypeptide comprising or consisting of one or more Derp 1-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA- DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 6-283; 682-723;iii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite polypeptide selected from the group consisting of: (a”)-(c”), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01;a ”) SEQ ID NO: 284;b ”) SEQ ID NO: 285; andc ”) SEQ ID NO: 286;iv) a polypeptide comprising or consisting of one or more Der f 1-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 287-448;v) a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01;vi) a polypeptide comprising or consisting of one or more Der p 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 450-534; 724-743;vii)a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide of SEQ ID NO: 535, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01;viii)a polypeptide comprising or consisting of one or more Der f 2-derived HLA-binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA- DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 536-620;ix) a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01;x) a polypeptide comprising or consisting of one or more Der p 23-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 622-647;xi) a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NO: 744, preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01;xii)a polypeptide comprising or consisting of one or more Der f 23-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / orHLA- DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 649-672;c) optionally, a nucleic acid sequence encoding for one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673; d) a nucleic acid sequence encoding for, preferably in the following order:d’) one or more transmembrane domains, preferably derived from LAMP-1 , LAMP- 2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; andd”) one or more cytosolic domains, preferably derived from LAMP-1 , LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1;preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) have a sequence identity of at least 75% to SEQ ID NO: 674 or SEQ ID NO: 675; further preferably, said one or more transmembrane domains comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.The nucleic acid construct of any one of the preceding embodiments, wherein said construct encoding for an enzymatically inactive polypeptide.The nucleic acid construct of any one of the preceding embodiments, wherein said construct encoding for one or more polypeptide / s comprising or consisting of polypeptide / s selected from the group consisting of: SEQ ID NOs: 676-681, 682-723, 724-743.The nucleic acid construct of any one of the preceding embodiments, wherein said nucleic acid is a RNA molecule, preferably a mRNA molecule, further preferably said RNA is a monocistronic or polycistronic mRNA molecule, preferably, a polycistronic mRNA molecule encodes for at least two polypeptides differing for the respective sequences b.The nucleic acid construct of any one of the preceding embodiments, wherein said nucleic acid comprises one or more modified nucleosides, preferably said one or more modified nucleosides are selected from the group consisting of:a) m1lP (1-methylpseudouridine);b) rr^acp3^ (1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine);c) ^Pm (2'-0-methylpseudouridine);d) m5D (5-methyldihydrouridine);e) m3^ (3-methylpseudouridine); and / orf) any combination thereof.The nucleic acid construct of any one of the preceding embodiments, wherein said nucleic acid is engineered or modified to direct the encoded polypeptide to endolysosomal compartments within a cell (e.g., a human cell), preferably, said nucleic acid encodes an endo-lysosomal-targeted polypeptide.A polypeptide comprising or consisting of the following sequence (b) and, optionally, one or more (e.g., 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the following sequences (a), (c), (d), preferably in the following order:a) a signal polypeptide, preferably derived from an N-terminal polypeptide fragment of human or murine LAMP-1 (e.g., having a Uniprot accession number: Q8VH34), further preferably the polypeptide fragment is at least 15 amino acids long, even further preferably the signal polypeptide has at least 75% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, most preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2;b) one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) house dust mite polypeptides, preferably allergens, wherein said polypeptides comprising one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc.) of the following (i)-(xii) or selected from the group consisting of (i)-(xii):i) a polypeptide having at least 80% sequence identity to Der p 1 house dust mite polypeptide selected from the group consisting of: (a’)-(c’), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01; HLA-DRB1*07:01; HLA-DRB1*15:01; HLA-DRB3*01:01; HLA- DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01;a ) SEQ ID NO: 5;b ) SEQ ID NO: 4; andc) SEQ ID NO: 3;ii) a polypeptide comprising or consisting of one or more Der p 1-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01; HLA-DRB1*07:01; HLA- DRB1*15:01; HLA-DRB3*01:01; HLA-DRB3*02:02; HLA-DRB4*01:01; and / or HLA-DRB5*01:01; wherein said one or more Der p 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 6-283; 682-723;iii) a polypeptide having at least 80% sequence identity to Der f 1 house dust mite polypeptide selected from the group consisting of: (a”)-(c”), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01:a ”) SEQ ID NO: 284;b ”) SEQ ID NO: 285; andc ”) SEQ ID NO: 286;iv) a polypeptide comprising or consisting of one or more Der f 1 -derived H LA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 1-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 287-448;v) a polypeptide having at least 80% sequence identity to Der p 2 house dust mite polypeptide selected from the group consisting of: (a’”), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01:a ”’) SEQ ID NO: 449;vi) a polypeptide comprising or consisting of one or more Der p 2-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der p 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 450-534; 724-743; vii) a polypeptide having at least 80% sequence identity to Der f 2 house dust mite polypeptide selected from the group consisting of: (a””), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01;a ” ”) SEQ ID NO: 535;viii) a polypeptide comprising or consisting of one or more Der f 2-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 2-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 536-620;ix) a polypeptide having at least 80% sequence identity to Der p 23 house dust mite polypeptide selected from the group consisting of: (a’””), preferably said polypeptide has an antigenic specificity presented in the context of: HLA- DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA- DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01:a ’”) SEQ ID NO: 621;x) a polypeptide comprising or consisting of one or more Der p 23-derived H LA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der p 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 622-647;xi) a polypeptide having at least 80% sequence identity to Der f 23 house dust mite polypeptide sequence identity to Der f 23 house dust mite polypeptide selected from the group consisting of: (a”””), preferably said polypeptide has an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and / or HLA-DRB5*01:01;a ”’) SEQ ID NO: 744;xii) a polypeptide comprising or consisting of one or more Der f 23-derived HLA- binding peptides, preferably said polypeptide / s have an antigenic specificity presented in the context of: HLA-DRB1*03:01, HLA-DRB1*07:01, HLA- DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01 :01 and / or HLA-DRB5*01:01; wherein said one or more Der f 23-derived HLA-binding peptides selected from the group consisting of: SEQ ID NOs: 649-672;c) optionally, one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673;d) one or more transmembrane domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; and one or more cytosolic domains, preferably derived from LAMP-1, LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1; preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.The polypeptide of any one of the preceding embodiments, wherein said polypeptide comprising or consisting of one or more polypeptide / s selected from the group consisting of: SEQ ID NOs: 676-681, 682-723, and 724-743.An isolated host cell, plurality of said isolated host cells, lipid nanoparticles (LNPs) or polymersomes comprising and / or expressing one or more of the nucleic acid construct / s and / or one or more of the polypeptides of any one of the preceding embodiments.A composition comprising one or more of the nucleic acid construct / s, polypeptide / s, cell / s, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of any one of the preceding embodiments, preferably said composition is a diagnostic, pharmaceutical composition, immune-therapeutical composition, allergen immunotherapy (AIT) composition, in vitro transcription composition (IVT composition), delivery composition and / or vaccine composition, further preferably said composition is selected from a group consisting: AIT-, IVT- and vaccine composition, most preferably said said composition is a vaccine composition.A composition comprising one or more nucleic acid constructs according to any one of embodiments 1 to 6 and / or one or more nucleic acids, preferably RNA / s, most preferably mRNA / s, encoding polypeptides according to embodiment 7 or 8, the encoded polypeptides differing from each other for at least the respective sequences b, preferably, all nucleic acids are encapsulated in lipid nanoparticles, further preferably, nucleic acids differing from each other for the respective nucleobases sequences are encapsulated in respective lipid nanoparticles, optionally, the lipid nanoparticles encapsulating the differing nucleic acids have the same composition in terms of constituting lipids.The composition according to embodiment 11, whereinthe b sequence of a first polypeptide of said polypeptides is selected from the group consisting of:the polypeptide comprising or consisting of the one or more Der p 1 -derived H LA- binding peptides; the polypeptide comprising or consisting of the one or more Der f 1- derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides;the b sequence of a second polypeptide of said polypeptides is selected from the group consisting of:the polypeptide comprising or consisting of the one or more Der p 1 -derived H LA- binding peptides; the polypeptide comprising or consisting of the one or more Der p 2- derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der f 1-derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der f 2-derived HLA-binding peptides; and the polypeptide comprising or consisting of the one or more Der f 23-derived HLA-binding peptides;andthe b sequence of an optional third polypeptide of said polypeptides is selected from the group consisting of:the polypeptide comprising or consisting of the one or more Der p 1-derived HLA- binding peptides; the polypeptide comprising or consisting of the one or more Der p 2- derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides; the polypeptide comprising or consisting of the one or more Der f 1-derived HLA-binding peptides; and the polypeptide comprising or consisting of the one or more Der f 23-derived HLA-binding peptides;preferably,the b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the b sequence of the third polypeptide is the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides; orthe b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der f 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der f 2-derived HLA-binding peptides; and the b sequence of the third polypeptide is the polypeptide comprising or consisting of the one or more Der f 23-derived HLA-binding peptides; orthe b sequence of the first polypeptide and, when included, of the third optional polypeptide are polypeptides comprising or consisting of the one or moreDer p 1-derived HLA-binding peptides; and the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der f 1-derived HLA-binding peptides; orthe b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der f 2-derived HLA-binding peptides; orthe b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides; and the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der f 23-derived HLA-binding peptides; orthe b sequences of the first polypeptide, the second polypeptide, and the third polypeptide are polypeptides comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; orthe b sequences of the first polypeptide, the second polypeptide, and the third polypeptide are polypeptides comprising or consisting of the one or more Der p 2-derived HLA-binding peptides;the b sequences of the first polypeptide, the second polypeptide, and the third polypeptide are polypeptides comprising or consisting of the one or more Der p 23-derived HLA-binding peptides; orthe b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the b sequence of the third polypeptide is the polypeptide comprising or consisting of the one or more Derf 1-derived HLA-binding peptides;more preferably,the b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the b sequence of the third polypeptide is the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides orthe b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; the b sequence of thethird polypeptide is the polypeptide comprising or consisting of the one or more Der p 23-derived H LA-binding peptides;most preferably, the b sequence of the first polypeptide is the polypeptide comprising or consisting of the one or more Der p 1-derived HLA-binding peptides; the b sequence of the second polypeptide is the polypeptide comprising or consisting of the one or more Der p 2-derived HLA-binding peptides; and the b sequence of the third polypeptide is the polypeptide comprising or consisting of the one or more Der p 23-derived HLA-binding peptides.The composition according to embodiment 12, wherein the first, second, and / or third polypeptide is a polypeptide further including the signal polypeptide (a) and the transmembrane and cytosolic domains (d); preferably, each one of the first, second and third polypeptides is a polypeptide further including the signal polypeptide (a) and the transmembrane and cytosolic domains (d), further preferably, each one of the first, second, and third polypeptides is selected from the group consisting of SEQ ID NOs: 676- 681.The composition according to embodiment 12, wherein the first polypeptide, the second polypeptide, and / or the third polypeptides is a peptide consisting of one or more respective HLA-binding peptides; preferably, the first polypeptide, the second polypeptide, and / or the third polypeptide is a peptide consisting of one of the respective HLA-binding peptides; most preferably, each of the first polypeptide, the second polypeptide, and the third polypeptide is a peptide consisting of one of the respective HLA-binding peptides.The nucleic acid construct, polypeptide, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of any one of the preceding embodiments, for use as a medicament and / or in therapy.The nucleic acid construct, polypeptide, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of any one of the preceding embodiments, for use in one or more of the following methods:a) method for treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy;b) method for increasing tolerance to dust mites;c) method for reducing a serum allergen-specific I g E level in a subject; and / ord) any combination of methods as in (a)-(c).

[0151] It is noted that as used herein, the singular forms “a”, “an”, and “the”, include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “a reagent” includes one or more of such different reagents and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein.

[0152] Unless otherwise indicated, the term "at least" preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.

[0153] The term "and / or" wherever used herein includes the meaning of "and", "or" and "all or any other combination of the elements connected by said term".

[0154] The term “less than” or in turn “more than” does not include the concrete number.

[0155] For example, less than 20 means less than the number indicated. Similarly, more than or greater than means more than or greater than the indicated number, e.g., more than 80 % means more than or greater than the indicated number of 80 %.

[0156] Throughout this specification and the items which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. When used herein the term “comprising” can be substituted with the term “containing” or “including” or sometimes when used herein with the term “having”. When used herein “consisting of" excludes any element, step, or ingredient not specified.

[0157] The term “including” means “including but not limited to”. “Including” and “including but not limited to” are used interchangeably.

[0158] It should be understood that this invention is not limited to the particular methodology, protocols, material, reagents, and substances, etc., described herein and as such can vary. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention, which is defined solely by the items.

[0159] All publications cited throughout the text of this specification (including all patents, patent application, scientific publications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. To the extent the material incorporated by reference contradicts or is inconsistent with this specification, the specification will supersede any such material.

[0160] The content of all documents and patent documents cited herein is incorporated by reference in their entirety.EXAMPLES OF THE INVENTION

[0161] An even better understanding of the present invention and of its advantages will be evident from the following examples, offered for illustrative purposes only. The examples are not intended to limit the scope of the present invention in any way.

[0162] Example 1:

[0163] Material and methods:

[0164] Murine model

[0165] Female C57BL6 / J mice aged 5-8 weeks (Charles River, Sulzfeld, Germany) were housed under specific pathogen-free conditions with food and water ad libitum. All experiments were approved by the government of the district of Upper Bavaria (ethical approvals: 55.2-2532.Vet_02-20-098) and carried out under the federal guidelines for the use and care of laboratory animals.

[0166] Allergic and AIT-treated mice were i.n. -sensitized with 1 pg (total protein content) HDM extract (Der p) in 20 pl PBS on three consecutive days followed by i.n. challenges with 10 pg HDM extract on days 8, 13, and 19. Nonallergic mice received 20 pl PBS i.n. AIT was performed with s.c. injections of either 440 pg HDM extract or LNPs (50 mol% ionizable lipid, 37.5-38.5 mol% cholesterol (here used 37.5 mol%), 10 mol% DSPC, and 1.5-2.5 mol% PEG-lipid (here used 2.5 mol%) with individually packaged allergen coding mRNAs (Der p 1, Der p 2 & Der p 23) with a dose of 5 pg per mRNA in 200 pl PBS on days 15, 18, and 22. Not AIT-treated allergic and nonallergic mice received s.c. injections of 200 pl PBS. All mice were challenged i.n. with 10 pg HDM extract on days 30, 31, 32 and 33 and euthanized at day 34 for analysis. The polypeptides encoded by the mRNA used in the Example 1 are the ones shown in Figure 1A, according to SEQ ID NOs: 745-747.

[0167] Cell Isolation (BAL + Leukocytes)

[0168] For isolation of bronchoalveolar lavage (BAL) cells, the chest of euthanized mice was opened, the trachea cannulated and airways lavaged five times with 0.8 mL PBS. BAL cells were further analyzed via flow cytometry. To isolate pulmonary leukocytes, lungs were removed and digested in digestion buffer (RPMI medium (Thermo Fisher Scientific) containing 1 mg / mL collagenase A and 100 pg / mL DNAse I (both from Sigma-Aldrich, Merck, Darmstadt, Germany) using the pre-programmed lung tissue digestion protocol of the gentleMACS dissociator and incubation for 30 min at 37° C. Digested lung tissue was mashed trough a 70 pm cell strainer. Cells were pelleted (400 g, 4 °C, 5 min), resuspended in 5 mL 40% percoll in RPMI (v / v) solution, underlayered with 5 mL 80% percoll solution, and centrifuged (1600 g, RT, 15 min). Lymphocyteswere collected from the interphase and washed with PBS. Finally red blood cells were lysed with ACK buffer for 2 min.

[0169] FACS Analysis

[0170] Isolated BALF cells were treated with Fc block for 10 min at 4°C and then stained with a fixable viability dye for 10 min at 4° C. Cells were washed twice with FACS buffer (1 % FCS in PBS) and labeled with antibodies against surface markers for 20 min at 4° C. Stained cells were washed twice and resuspended in FACS buffer, and analyzed using an LSRFortessa™ flow cytometer.

[0171] Pulmonary lymphocytes were treated with Fc block for 10 min at 4°C and then stained with a fixable viability dye (for 10 min at 4° C to exclude dead cells). Cells were washed twice with PBS and labeled with antibodies against surface markers for 20 min at 4° C. Cells were washed twice with PBS and subsequently fixed with the eBioscienceTM FoxP3 / Transcription factor kit (Thermo Fisher Scientific) over night. After washing twice with fixation / permeabilization kit buffer, intracellular staining was performed for 1 h at room temperature. Cells were washed once with fixation / permeabilization kit buffer and FACS buffer, resuspended in FACS buffer, and analyzed using a BD LSRFortessa™ flow cytometer.

[0172] Antibody measurements

[0173] Serum levels of total lgG1, lgG2b, lgG2c and lgG3 levels were analyzed using the LEGENDplex™ Mouse Immunoglobulin Isotyping Panel (BioLegend) according to the manufacturer’s instructions. For the detection of Der p-specific lgG1, plates were coated with goat-anti-mouse IgG 1 (Citeq) followed by incubation with mouse sera. Der p-slgG1 was detected with a biotinylated Der p extract (Citeq). Quantification of total IgE (tlgE) was performed with the BD Mouse IgE ELISA set (BD Biosciences) following the manufacturer’s instructions. For the detection of Der p-specific IgE, plates were coated with IgE capture antibody (BD Biosciences) followed by incubation with mouse sera. Der p-sIgE was detected with a biotinylated Der p extract (Citeq).

[0174] Results

[0175] The following results as shown in Figure 3-6 habe been obtained with the exemplary constructs of the present invention (Der p 1 , Der p 2 & Der p 23) as carried out according to the procedures outlined above and in Figures 1-2.

[0176] Figure 3 shows the quantification of the absolute cell counts and numbers of eosinophils, alveolar macrophages, CD4+ lymphocytes, CD8+ lymphocytes and natural killer cells (NK cells) in the bronchoalveolar lavage at the end of the experiment (day 34). The respective cell populations show a significant increase after sensitization and subsequent allergen challenge of the animals without therapy (HDM-allergic) compared to the control group (non-allergic), reflecting a high cell infiltration induced by the allergic inflammation. The applied mRNAAIT of the present invention can significantly reduce the effect of this allergic inflammation by reducing cell infiltration (lower total cell count and reduced cell count of specific effector cells). This contrasts with classic extract AIT, which only leads to a slight reduction in the total cell count and eosinophils. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; BALF, bronchoalveolar lavage; HDM, house dust mite.

[0177] Figure 4 shows the quantification of GATA3+CD4+ T cells (Th2 cells) as a percentage of total CD4+ T cells in lung tissue at the end of the experiment (day 34). Th2 cell-driven allergic inflammation is a central molecular component underlying type 1 allergy (e.g. house dust mite allergy). An increase in this specific T cell population can be seen after allergic sensitization and subsequent provocation. mRNA AIT of the present invention leads to a significant reduction of this disease-associated cell population to a level similar to that observed in the control group (non-allergic). In contrast, extract AIT seems to have no effect. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; HDM, house dust mite.

[0178] Figure 5 shows the level of total (concentration) and house dust mite-specific (OD) IgE antibodies in serum at the end of the experiment (day 34). IgE is considered to be another central molecular component in direct type 1 hyperreactivity reactions. Allergen provocation after previous sensitization leads to a significant increase in allergen-specific IgE in addition to an increase in total IgE in serum. This increase in IgE titer associated with HDM allergy can be significantly reduced by mRNA therapy to the same extent as classical extract AIT. Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; Der p, Dermatophagoides pteronyssinus; HDM, house dust mite; OD, optical density.

[0179] Figure 6 shows the level of house dust mite-specific lgG1 antibodies as well as total lgG1, lgG2c, lgG2band lgG3 antibodies in serum at the end of the experiment (day 34). Part of a successful AIT therapy is considered to be the shift from an IgE dominated to a more IgG mediated humoral response. We can observe this type of shift in the course of mRNA AIT. This leads to a significant increase in the p-specific lgG1 as well as the total lgG1 and lgG2c titres. This significant increase is also observed in the course of classic AIT (extract AIT), but to a lesser extent. In addition, only the mRNA AIT leads to a significant reduction in the total lgG3 titer compared to the allergic group (HDM-allergic). Statistical analyses were performed using the Mann-Whitney test, p-values of < .05, < .01, < .001, < .0001 are shown as *, **, ***, ****. AIT, allergen-specific immunotherapy; Der p, Dermatophagoides pteronyssinus; HDM, house dust mite; OD, optical density.

[0180] Example 2:

[0181] Methods

[0182] Generation of Der p 1 and Der p 2 specific T-cell lines

[0183] Der p 1 or Der p 2 specific TCL were obtained according to a procedure as previously described (Kahlertetal., 1999; Schramm et al., 1999) by initial seeding of 1x105PBMC and 5 pg / ml nDer p 1or 4 pg / ml nDer p 2 respectively in Ultraculture medium (Lonza, Verviex, Belgium) supplemented with 2 mM UltraGlutamine I (Lonza, Verviex, Belgium) antibiotic-antimycotic solution (Sigma, Taufkirchen, Germany) and 20 M p-mercaptoethanol (Invitrogen, ) in 100 l volume in a 96-well round-bottom culture plate. Cultures were fed twice after 6 and 9 days with IL-2 (10-25 U / ml; Miltenyi Biotec, Bergisch-Gladbach, Germany) before a proliferation assay was performed 12 to 14 days after starting the culture. TCL with a stimulation index (SI) > 2 were considered as positive. Positive TCL received another stimulation with Der p 1 or Der p 2 respectively and mitomycin c-treated autologous PBMC, and were transferred to a 48-well culture plate. TCL were stimulated with IL-2 every 3 to 4 days, and after 12 to 14 days a second proliferation test was performed. Positive TCL were further expanded under alternating stimulation at first with allergen and mitomycin c-treated autologous PBMC and then with phytohaemagglutinin and mitomycin c-treated allogenous PBMC (a mixture of PBMC from 3 non-allergic donors).

[0184] Proliferation assay

[0185] T-cells were seeded in triplicate at 2 x 104cells / well in 96-well round-bottom culture plates under stimulation with the Dermatophagoides allergen extracts in a concentration 10 PNU / ml, 100 PNU / ml and 1000 PNU / ml and 5 x 104mitomycin-c treated autologous PBMC or 5 x 103moDC. After 48 h incubation 1 pCi 3H-thymidine (PerkinElmer, Rodgau-Jugesheim, Germany) was added to each well and the plates were further incubated for 16 h. Cells were then harvested on Microbeta filter mats with a 96-well cell harvester (PerkinElmer). After drying, the filter mats were prepared for counting by melting the solid scintillator Meltilex using a microplate heatsealer (PerkinElmer). Counting was performed in a Microbeta scintillation counter (PerkinElmer). The stimulation index (SI) was calculated as the quotient of counts per minute (cpm) of the allergen stimulated cells (T-cells, APC, allergen) and the unstimulated control cells (T-cells, APC, without allergen).

[0186] Characterization of Der p 1 and Der p 2-reactive TCL

[0187] The Der p 1 and Der p 2-specific TCL were characterized by epitope mapping with synthetic peptides. Peptides were synthesized by solid-phase synthesis on polyethylene pins as previously described (Schramm et al., 1999). A total of 71 Der p 1 (isoform Der p 1.0105) and 40 Der p 2 (isoform Der p 2 .0114) 12-mer peptides overlapping by nine amino acids, spanned the amino acid sequences of the respective molecules. In stimulation assays T-cells peptides were used at a concentration of 2 pg / ml.

[0188] Der p 1 T cell line epitopes

[0189] Table 2: The epitopes of Der p 1 specific T cell lines from allergic donors, generated and analysed are indicated by the position of the amino acids in the sequence starting from the N-terminus (see also Figures 7, 8).Epitop Epitop EpitopeStart End Sequence SEQ ID NOs:1 11 TNACSINGNAP 6821 12 TNACSINGNAPA 68310 21 APAEIDLRQMRT 68413 24 EIDLRQMRTVTP 68513 25 EIDLRQMRTVTPI 68616 27 LRQMRTVTPIRM 68719 30 MRTVTPIRMQGG 68822 31 VTPIRMQGGC 68928 39 QGGCGSCWAFSG 69028 45 QGGCGSCWAFSGVAATES 69134 45 CWAFSGVAATES 69240 51 VAATESAYLAYR 69352 66 NQSLDLAEQELVDCA 69455 66 NQSLDLAEQELVDCA 69579 93 GIEYIQHNGWQESY 69682 93 YIQHNGVVQESY 69785 96 HNGVVQESYYRY 69885 99 HNGVVQESYYRYVAR 69988 99 VVQESYYRYVAR 70091 102 ESYYRYVAREQS 701106 123 PNAQRFGISNYCQIYPPN 702109 123 QRFGISNYCQIYPPN 703115 126 NYCQIYPPNVNK 704122 135 PNVNKIREALAQTH 705124 139 VNKIREALAQTHSAIA 706130 145 ALAQTHSAIAVIIGIK 707139 150 AVIIGIKDLDAF 708145 156 KDLDAFRHYDGR 709145 159 KDLDAFRHYDGRTII 710148 160 DAFRHYDGRTIIQ 711151 168 RHYDGRTIIQRDNGYQPN 712151 162 RHYDGRTIIQRD 713157 168 TIIQRDNGYQPN 714163 174 NGYQPNYHAVNI 715166 186 QPNYHAVNIVGYSNAQGVDYW 716169 183 YHAVNIVGYSNAQGV 717172 183 VNIVGYSNAQGV 718172 184 VNIVGYSNAQGVDYW 719172 186 VNIVGYSNAQGVD 720175 189 VGYSNAQGVDYWIVR 721199 211 NGYGYFAANIDLM 722209 219 DLMMIEEYPYV 723

[0190] Der p 2 T cell line epitopes

[0191] Table 3: The epitopes of Der p 2 specific T cell lines from allergic donors, generated, are indicated by the position of the amino acids in the sequence starting from the N-terminus (see also Figures 7, 8).Epitope Epitope EpitopeStart End Sequence SEQ ID NOs:1 15 DQVDVKDCANHEIKK 72422 33 HGSEPCIIHRGK 72522 33 HGSEPCIIHRGK 72622 36 HGSEPCIIHRGKPFQ 72722 39 HGSEPCIIHRGKPFQLEA 72825 39 EPCIIHRGKPFQLEA 72925 42 EPCIIHRGKPFQLEALFE 73037 51 LEALFEANQNTKNAK 73137 51 LEALFEANQNTKNAK 73237 51 LEALFEANQNTKNAK 73337 51 LEALFEANQNTKNAKIEIKASIDG (+49-60 734Epitop corresponding to SEQ ID NO: 748)40 51 LFEANQNTKNAK 73546 57 NTKNAKIEIKAS 73664 84 DVPGIDPNACHYVKCPLVKGQ 73767 81 GIDPNACHYVKCPLV 73870 84 PNACHYVKCPLVKGQ 73985 99 QYDIKYTWNVPKIAP 74094 105 VPKIAPKSENVV 74197 111 VPKIAPKSENVVVTVKVL 742115 126 GVLACAIATHAK 743

[0192] Example 3: Further exemplary LNP transfection of PBMC and quantification of cytokines:

[0193] Methods

[0194] Optimized mRNA constructs and corresponding protein sequences used in this example encode for cysteine protease mutants and contain human LAMP-1 instead of murine LAMP-1:

[0195] SEQ ID NO: 749 (Sequence Pro-Der p 1.0102 C132A - LAMP-1):MAAPGSARRPLLLLLLLLLLGLMHCASARPSSIKTFEEYKKAFNKSYATFEDEEAARKNFLESVK YVQSNGGAINHLSDLSLDEFKNRFLMSAEAFEHLKTQFDLNAETNACSINGNAPAEIDLRQM RT VTPIRMQGGCGSAWAFSGVAATESAYLAYRNQSLDLAEQELVDCASQHGCHGDTIPRGIEYIQ HNGVVQESYYRYVAREQSCRRPNAQRFGISNYCQIYPPNVNKIREALAQTHSAIAVIIGIKDLDA FRHYDGRTIIQRDNGYQPNYHAVNIVGYSNAQGVDYWIVRNSWDTNWGDNGYGYFAANIDLMM\EEYPW / \ / \LGGGGSMLIPIAVGGALAGLVUVUAYLVGRKRSHAGYQTI

[0196] SEQ ID NO: 750 (corresponding RNA construct for SEQ ID NO: 749): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctg ggcctgatgcactgcgccagcgccagacccagcagcatcaagaccttcgaggagtacaag aaggccttcaacaagagctacgccaccttcgaggacgaggaggccgccagaaagaacttc ctggagagcgtgaagtacgtgcagagcaacggcggcgccatcaaccacctgagcgacctg agcctggacgagttcaagaacagattcctgatgagcgccgaggccttcgagcacctgaag acccagttcgacctgaacgccgagaccaacgcctgcagcatcaacggcaacgcccccgcc gagatcgacctgagacagatgagaaccgtgacccccatcagaatgcagggcggctgcggc agcgcctgggccttcagcggcgtggccgccaccgagagcgcctacctggcctacagaaac cagagcctggacctggccgagcaggagctggtggactgcgccagccagcacggctgccac ggcgacaccatccccagaggcatcgagtacatccagcacaacggcgtggtgcaggagagc tactacagatacgtggccagagagcagagctgcagaagacccaacgcccagagattcggc atcagcaactactgccagatctacccccccaacgtgaacaagatcagagaggccctggcc cagacccacagcgccatcgccgtgatcatcggcatcaaggacctggacgccttcagacac tacgacggcagaaccatcatccagagagacaacggctaccagcccaactaccacgccgtg aacatcgtgggctacagcaacgcccagggcgtggactactggatcgtgagaaacagctgg gacaccaactggggcgacaacggctacggctacttcgccgccaacatcgacctgatgatg atcgaggagtacccctacgtggtgatcctgggcggcggcggcagcatgctgatccccatc gccgtgggcggcgccctggccggcctggtgctgatcgtgctgatcgcctacctggtgggc agaaagagaagccacgccggctaccagaccatctga

[0197] Full Length(1116bp) | A(24% 269) | T(14% 146) | G(29% 329) | 0(33% 372)

[0198] SEQ ID NO: 751 (Sequence Pro-Der f 1.0101 C133A - LAMP-1): MAAPGSARRPLLLLLLLLLLGLM HCASARPASI KTFEEFKKAFN KNYATVEEEEVARKN FLESLK YVEANKGAINHLSDLSLDEFKNRYLMSAEAFEQLKTQFDLNAETSACRINSVNVPSELDLRSLR TVTPIRMQGGCGSAWAFSGVAATESAYLAYRNTSLDLSEQELVDCASQHGCHGDTIPRGIEYIQ QNGVVEERSYPYVAREQQCRRPNSQHYGISNYCQIYPPDVKQIREALTQTHTAIAVIIGIKDLRAF QHYDGRTIIQHDNGYQPNYHAVNIVGYGSTQGVDYWIVRNSWDTTWGDSGYGYFQAGNNLMM\EQYPY\ / \ / \MGGGGSMUPIAVGGALAGLVLIVUAYLVGRKRSHAGYQTI

[0199] SEQ ID NO: 752 (corresponding RNA construct for SEQ ID NO: 751): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctgggcctgatgcactgcgccagcgccag acccgccagcatcaagaccttcgaggagttcaagaaggccttcaacaagaactacgccaccgtggaggaggaggaggtggcca gaaagaacttcctggagagcctgaagtacgtggaggccaacaagggcgccatcaaccacctgagcgacctgagcctggacgagt tcaagaacagatacctgatgagcgccgaggccttcgagcagctgaagacccagttcgacctgaacgccgagaccagcgcctgca gaatcaacagcgtgaacgtgcccagcgagctggacctgagaagcctgagaaccgtgacccccatcagaatgcagggcggctgc ggcagcgcctgggccttcagcggcgtggccgccaccgagagcgcctacctggcctacagaaacaccagcctggacctgagcgag caggagctggtggactgcgccagccagcacggctgccacggcgacaccatccccagaggcatcgagtacatccagcagaacgg cgtggtggaggagagaagctacccctacgtggccagagagcagcagtgcagaagacccaacagccagcactacggcatcagc aactactgccagatctacccccccgacgtgaagcagatcagagaggccctgacccagacccacaccgccatcgccgtgatcatcg gcatcaaggacctgagagccttccagcactacgacggcagaaccatcatccagcacgacaacggctaccagcccaactaccacg ccgtgaacatcgtgggctacggcagcacccagggcgtggactactggatcgtgagaaacagctgggacaccacctggggcgaca gcggctacggctacttccaggccggcaacaacctgatgatgatcgagcagtacccctacgtggtgatcatgggcggcggcggcagc atgctgatccccatcgccgtgggcggcgccctggccggcctggtgctgatcgtgctgatcgcctacctggtgggcagaaagagaagc cacgccggctaccagaccatctga

[0200] Full Length(1119bp) | A(23% 268) | T(15% 145) | G(30% 337) | C(32% 369)

[0201] SEQ ID NO: 753 (Sequence Der p 2.0110 - LAMP-1):MAAPGSARRPLLLLLLLLLLGLMHCASADQVDVKDCAN H El KKVLVPGCHGSEPCI I H RGKPFQ LEAVFEANQNSKTAKI El KASI DGLEVDVPGI DPNACHYM KCPLVKGQQYDI KYTWN VPKI APKS ENWVTVKVMGDNGVLACAIATHAKIRDGGGGS / WL / P / AV'GGALAGLV'L / V'L / AYLV'GR RSHAG YQTI SEQ ID NO: 754 (corresponding RNA construct for SEQ ID NO: 753): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctgggcctgatgcactgcgccagcgccga ccaggtggacgtgaaggactgcgccaaccacgagatcaagaaggtgctggtgcccggctgccacggcagcgagccctgcatcat ccacagaggcaagcccttccagctggaggccgtgttcgaggccaaccagaacagcaagaccgccaagatcgagatcaaggcca gcatcgacggcctggaggtggacgtgcccggcatcgaccccaacgcctgccactacatgaagtgccccctggtgaagggccagc agtacgacatcaagtacacctggaacgtgcccaagatcgcccccaagagcgagaacgtggtggtgaccgtgaaggtgatgggcg acaacggcgtgctggcctgcgccatcgccacccacgccaagatcagagacggcggcggcggcagcatgctgatccccatcgccg tgggcggcgccctggccggcctggtgctgatcgtgctgatcgcctacctggtgggcagaaagagaagccacgccggctaccagac catctga

[0202] Full Length(597bp) | A(20% 125) | T(15% 80) | G(32% 192) | 0(33% 200)

[0203] SEQ ID NO: 755 (Sequence Der f 2.0102 - LAMP-1):MAAPGSARRPLLLLLLLLLLGLMHCASADQVDVKDCANNEIKKVMVDGCHGSDPCIIHRGKPFT LEALFDANQNTKTAKIEIKASLDGLEIDVPGIDTNACHFMKCPLVKGQQYDIKYTWNVPKIAPKSE NYYYTYKUGDNGYLACMATHGKIRDGGGGSMUPIAVGGALAGLVUVUAYLVGRKRSHAGYQTlSEQ ID NO: 756 (corresponding RNA construct for SEQ ID NO: 755): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctgggcctgatgcactgcgccagcgccga ccaggtggacgtgaaggactgcgccaacaacgagatcaagaaggtgatggtggacggctgccacggcagcgacccctgcatcat ccacagaggcaagcccttcaccctggaggccctgttcgacgccaaccagaacaccaagaccgccaagatcgagatcaaggcca gcctggacggcctggagatcgacgtgcccggcatcgacaccaacgcctgccacttcatgaagtgccccctggtgaagggccagca gtacgacatcaagtacacctggaacgtgcccaagatcgcccccaagagcgagaacgtggtggtgaccgtgaagctgatcggcga caacggcgtgctggcctgcgccatcgccacccacggcaagatcagagacggcggcggcggcagcatgctgatccccatcgccgt gggcggcgccctggccggcctggtgctgatcgtgctgatcgcctacctggtgggcagaaagagaagccacgccggctaccagacc atctga

[0204] Full Length(597bp) | A(21% 128) | T(15% 81) | G(31% 186) | C(33% 202)

[0205] SEQ ID NO: 757 (Sequence Der p 23.0101 - LAMP-1):MAAPGSARRPLLLLLLLLLLGLMHCASAANDNDDDPTTTVHPTTTEQPDDKFECPSRFGYFAD PKDPHKFYICSNWEAVHKDCPGNTRWNEDEETCTGGGGS / WL / P / AV,GGALAGL\ / L / \ZL / AYLV,G RKRSHAGYQTI SEQ ID NO: 758 (corresponding RNA construct for SEQ ID NO: 757): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctgggcctgatgcactgcgccagcgccgcc aacgacaacgacgacgaccccaccaccaccgtgcaccccaccaccaccgagcagcccgacgacaagttcgagtgccccagca gattcggctacttcgccgaccccaaggacccccacaagttctacatctgcagcaactgggaggccgtgcacaaggactgccccggc aacaccagatggaacgaggacgaggagacctgcaccggcggcggcggcagcatgctgatccccatcgccgtgggcggcgccct ggccggcctggtgctgatcgtgctgatcgcctacctggtgggcagaaagagaagccacgccggctaccagaccatctga

[0206] Full Length(417bp) | A(20% 85) | T(14% 52) | G(29% 122) | 0(37% 158)

[0207] SEQ ID NO: 759 (Sequence Der f 23.0201 - LAMP-1):MAAPGSARRPLLLLLLLLLLGLMHCASADIDHDDDPTTMIDVQTTTVQPSDEFECPTRFGYFAD PKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCTGGGGS / WL / P / AV,GGALAGL\ / L / \ZL / AYLV,GR KRSHAGYQTI SEQ ID NO: 760 (corresponding RNA construct for SEQ ID NO: 759): atggccgcccccggcagcgccagaagacccctgctgctgctgctgctgctgctgctgctgggcctgatgcactgcgccagcgccga catcgaccacgacgacgaccccaccaccatgatcgacgtgcagaccaccaccgtgcagcccagcgacgagttcgagtgccccac cagattcggctacttcgccgaccccaaggacccctgcaagttctacatctgcagcaactgggaggccatccacaagagctgccccggcaacaccagatggaacgagaaggagctgacctgcaccggcggcggcggcagcatgctgatccccatcgccgtgggcggcgcc ctggccggcctggtgctgatcgtgctgatcgcctacctggtgggcagaaagagaagccacgccggctaccagaccatctga

[0208] Full Length(420bp) | A(20% 84) | T(15% 58) | G(29% 123) | 0(36% 155)

[0209] Blood sample collection and processing

[0210] For LNP testing in PBMCs, 4 healthy individuals and 7 individuals with house dust mite allergies were recruited from the pool of participants of an ongoing study following approval by the responsible ethics committee. Patients with allergies were identified by a positive history of symptomatic allergy and an enzyme allergosorbent test (EAST) class >3 (Euroline, Euroimmun, Lubeck, Germany). One blood donor showed weaker sensitization in the EAST with classes between 2 and 3. A negative history of allergy and EAST class 0 were used to select non-allergic participants as controls. Participants were 20-70 years old at the time of blood collection, received no corticosteroids in the 4 weeks before the blood donation, and were not under the effect of antihistamines.

[0211] LNP transfection of PBMC

[0212] Isolated PBMC were transferred to a 96-well plate (106cells / well) and transfected with 1.0 g of trivalent HDM mRNA-LNPs (LNP A or LNP B formulated with a different ionizable Lipid A- D; SEQ ID NOs: 749, 751, 753, 755, 757, 759). The 50% / 50% LNP A and LNP B mixture was also applied (LNP A+B). While trivalent LNP A contains mRNAs coding for allergens Der p 1 (SEQ ID NO: 749), Der p 2 (SEQ ID NO: 753) and Der p 23 (SEQ ID NO: 757), trivalent LNP B contains RNAs coding for allergens Derf 1 (SEQ ID NO: 751), Derf 2 (SEQ ID NO: 755), Der f 23 (SEQ ID NO: 759). The assessed LNP preparations A-D differ by the ionizable lipid. Transfection efficiency and expression of HDM allergens were assessed via flow cytometry 20 h post transfection. For intracellular HDM protein detection, cells were further restimulated with phorbol 12,13-dibutyrate (50 ng / mL) and ionomycin (500 ng / mL) in the presence of brefeldin A (5 pg / mL) and monensin (2 pM) at 37°C for 3-4 hours. Cells were stained for surface markers, including HLA-DR, CD14, CD11c, CD209 at RT for 30 minutes. In parallel, cells were stained with fixable viability dye Live / Dead Green. After washing with PBS, cells were fixed and permeabilized using the FoxP3 / Transcription Factor Staining Buffer Set (e-bioscience) according to the manufacturer’s instructions. Subsequently, cells were stained intracellularly with anti-HDM fluorescent antibody at RT for 30 min. Flow cytometry analysis was conducted on a BD FACSVerse machine with FACSuite analysis software.

[0213] Quantification of cytokines

[0214] PBMCs were exposed to HDM mRNA-LNPs for at least 20 hours. The cell culture supernatants were collected for cytokines quantification using the BioLegend LEGENDplex kit Human Th Cytokine Panel (Cat. No 741028) according to the manufacturer’s instructions. TheLEGENDplex assay captures molecules through beads with distinct sizes and fluorescence coated with capture antibodies that bind their specific analytes during incubation. Biotinylated detection antibodies and streptavidin-PE generate a fluorescence signal proportional to analyte levels. Flowcytometric separation of bead populations enables simultaneous and quantitative analyte detection. The absolute concentration of each factor was determined using the LEGENDplex data analysis software based on a standard curve recorded for each factor and run. Cytokine concentrations below the limit of detection (LOD) were assigned a value of zero for subsequent analyses.

[0215] Results:

[0216] After transfection with different HDM mRNA-LNP-constructs for 24 h human PBMCs were analysed via flow cytometry to show LNP-mediated antigen expression. As a representative example for antigen expression, Der p / f group 2 protein was intracellularly detected with a Der p / f group 2 specific PE-labeled antibody (Figure 9). Efficient antigen expression was found in the broader HLA-DR+cell population with 10-40%, compared to particularly high transfection rates within professional antigen-presenting cell subsets (CD209+ / CD11c+ / CD14+ / HLA-DR+), reaching 10-80%. It should be noted that the PBMCs were subjected to restimulation and Golgi-blockade, which may have influenced the protein expression levels. Taken together, these findings demonstrate that LNPs preferentially target endocytic APC populations, enabling robust antigen expression. Interestingly, successful transfection was detected in both allergic and non-allergic donors (data not shown).

[0217] After transfection of PBMCs from allergic and non-allergic donors with different HDM mRNA-LNP-constructs for 24 h, the cytokine secretion in the culture supernatant was analysed via Biolegend Legendplex. Representatively, the expression levels of two TH2 cytokines, IL-5 and IL-13, are shown in Figure 10. Supernatants from allergic PBMCs exhibited an induction of IL5 (Figure 10A) and IL13 (Figure 10C), whereas cells from non-allergic donors showed only minimal responses (Figure 10Aand 10D). Interestingly, high transfection efficiencies were detected in allergic and non-allergic donors indicating that functional differences in downstream cytokine secretion might derive from preexisting allergen-specific immune memory rather than a non-specific LNP effect. The observed selective cytokine upregulation strongly suggests an antigen presentation to allergen-specific cells, most probably TH2 cells. Consistently, different ionizable lipid formulations resulted in the same differential pattern, further supporting antigen-dependent recall activation restricted to allergic individuals.

[0218] Example 4: In vivo analysis in an animal model with human LAMP-1 fusion proteins and optimized inactive HDM group 1 allergen mutants in which the protease activity is abolished by a point mutation in the active site:

[0219] Optimized mRNA constructs and corresponding protein sequences used in this example are the same as in Example 3 above.

[0220] Methods

[0221] 1) Murine model

[0222] Female C57BL6 / J mice aged ~5 weeks (Charles River, Sulzfeld, Germany) were housed under specific pathogen-free conditions with food and water ad libitum. All experiments were approved by the government of the district of Upper Bavaria (ethical approvals: 55.2-2532.Vet_02-25-37) and carried out under the federal guidelines for the use and care of laboratory animals.

[0223] Female C57BL / 6J mice, 6-8 weeks old, were sensitized with a mixture of Dermatophagoides pteronyssinus (Der p) & Dermatophagoides farinae (Der f) HDM extract (Greer Laboratories Inc.; Der p, Cat#: XPB91D3A2.5, Lot#: 446803; Derf, Cat#:XPB81D3A2.5, Lot#: 435703) by 3 intranasal (i.n.) instillations on 3 consecutive days of 20 pl extract (reconstituted in 0,9% sterile NaCI and diluted in sterile PBS), 10 pl per nostril, containing a total protein content of 2 pg, 1 pg / species. Non-allergic mice received PBS. On days 7, 12 and 19 mice received further i.n. maintenance challenges as described for the sensitization. On days 14, 17 and 21 mice were treated subcutaneously (s.c.) with 200 pl of either sterile 0,9% NaCI (non-allergic, HDM-allergic) or different HDM mRNA-LNP preparations with 5 pg mRNA / allergen (L1, L2, L3, and L4, prepared as in Example 3 above). Finally, on days 29-32, all mice received i.n. challenges with HDM extract with a total protein content of 10 pg total protein, 5 pg / species. Mice were sacrificed on day 35 for further analysis. AIT, allergen-specific immunotherapy; Der f, Dermatophagoides farinae’, Der p, Dermatophagoides pteronyssinus’, HDM, house dust mite; i.n., intranasal; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; NaCI, sodium chloride; PBS, phosphate-buffered saline s.c., subcutaneous.

[0224] 2) Cell Isolation (BAL + lung lymphocytes)

[0225] For isolation of bronchoalveolar lavage (BAL) cells, the chest of euthanized mice was opened, the trachea cannulated and airways lavaged five times with 0.5 mL PBS. Cells were pelleted (xxx g, 4 °C, 5 min), the supernatant was collected ant frozen at -80 °C for further analysis and the cells were resuspended in 1 ml PBS and stored on ice until further processing. BAL cells were further analyzed via flow cytometry. To isolate pulmonary leukocytes, lungs were removed and digested in 5 ml digestion buffer (RPMI medium (Thermo Fisher Scientific) containing 1 mg / mL type IV collagenase and 100 pg / mL DNAse I (both from Sigma-Aldrich, Merck, Darmstadt, Germany) using the pre-programmed lung tissue digestion protocol (m_lung_01_02) of the gentleMACS dissociator followed by incubation for 30 min at 37 °C and shaking at 225 rpm, after which tissue was completely dissociated using the second-step program (m_lung_02_01). After adding 10 pl 0,5 MEDTA, digested lung tissue was mashed trough a 70 pm cell strainer. Cells were pelleted (450 g, 4 °C, 5 min), resuspended in 5 mL40% percoll in RPMI (v / v) solution, underlayered with 5 mL 80% percoll solution (v / v), and centrifuged (1600 g, RT, 15 min). Mononuclear cells were collected from the interphase and washed with PBS. Finally redblood cells were lysed with ACK buffer for 5 min at room temperature and washed twice with FACS buffer (2% FCS, 2 mM EDTA in PBS) and stored on ice until further processing.

[0226] 3) Lymphocyte stimulation

[0227] After red blood cell lysis, cells were resuspended in 100 l RPMI complete (RPMI1640, 10% FCS (v / v), 1% (v / v) Pen-Strep, 1% (v / v) L-Glutamine, 1% (v / v) non-essential aminoacids, 1% (v / v) Sodium Pyruvate, 5 pM beta-Mercaptoethanol), seeded onto 96-well, flatbottom plates. Then, 50 pl of stimulation medium (RPMI complete, 60 ng / ml PMA, 3pg / ml ionomycin) were added to a final concentration of 20 ng / ml PMA and 1 pg / ml ionomycin. After 1 h incubation at 37 °C (5% (v / v) CO2 and H2O saturated atmosphere), 50 pl of brefeldin A containing RPMI complete is added to a final concentration of 5 pg / ml brefeldin A, followed by another 3 h of incubation at 37 °C (5% (v / v) CO2 and H2O saturated atmosphere). Cells were then transferred to 96-well, V-bottom plates and washed 2 times with PBS for further processing, i.e. flow cytometric analysis.

[0228] 4) Flow cytometric analysis

[0229] Isolated BALF cells were transferred to 96-well, V-bottom plates and treated with Fc block (in PBS) for 10 min at 4 °C and then labeled with staining mix (in PBS) for 20 min at 4 °C stained. Cells were washed twice with FACS buffer (2% FCS, 2 mM EDTA in PBS) and resuspended in 100 pl FACS buffer, and analyzed using a BD LSRFortessa™ flow cytometer.

[0230] Pulmonary lymphocytes were treated with Fc block (in PBS) for 10 min at 4°C and then labeled with staining mix (in PBS) for 20 min at 4 °C stained. Cells were washed twice with PBS and subsequently fixed with the eBioscienceTM FoxP3 / Transcription factor kit (Thermo Fisher Scientific) according to manufacturer instructions. In short, cells are resuspended in 200 pl Fix / Perm concentrate (diluted 1:4 with Fix / Perm diluent), incubated for 20 miin at RT, washed twice with 200 pl permeabilization buffer (diluted 1:10 in ddH2O). Washing was followed by, intracellular staining overnight at 4 °C with staining mix in FACS buffer. The next day, cells were washed twice with permeabilization buffer diluted 1:10 in ddH2O), once with FACS buffer and finally resuspended in 100 pl FACS buffer for measurement using a BD LSRFortessa™ flow cytometer

[0231] 5) Antibody measurements

[0232] Serum levels of total lgG1, lgG2b, lgG2c and lgG3 levels were analyzed using the LEGENDplex™ Mouse Immunoglobulin Isotyping Panel (BioLegend) according to the manufacturer’s instructions. For the detection of Der p / f-specific lgG1 and lgG2c, 384-well plates (Thermo Fisher Scientific, 384-well, flat-bottom, transparent, MaxiSorp) were coated with 20 pl recombinant allergen solution (10 pg / ml in PBS) overnight at 4 °C. Plates were washed with 100 pl wash buffer (0,05% Tween-20 (v / v) in PBS) and blocked with 100 pl blocking buffer (4% biotin-free BSA (Carl Roth) in PBS) for 2 h at RT. After a washing step, 20 pl of with PBS diluted serum samples was added to the wells and incubated overnight at 4 °C. Blanks received onlyPBS. For lgG1 Serum was diluted 1:5000 and for lgG2c 1:2000. The next day, plates were washed 4 times, followed by a 2 h incubation with 20 pl of biotinylated anti-mouselgG1 (Southern Biotech [1144-08], 1:5000 in 1% biotin-free BSA in PBS) or biotinylated anti-mouselgG2c (BS [553388], 1:3000 in 1% biotin-free BSA in PBS). After 4 washing steps, 20 pl of strepavidin-HRP (Southern Biotech [7105-05], 1:6000 in biotin-free BSA in PBS) was added and incubated for 30 min at RT. Finally, after 4 washing steps 20 pl HRP-substrate was added. The development reaction was stopped by the addition of 10 pl 2 M H2SO4 and the ODs were measured at a light wavelength of 450 nm using a Tecan Infinite m200 Pro (Tecan).

[0233] Results and conclusions:

[0234] Figure 11 depicts the employed experimental model of house dust mite (HDM) induced allergic airway inflammation and allergen-specific immunotherapy (AIT). Female C57BL / 6J mice, 6-8 weeks old, were sensitized with a mixture of Dermatophagoides pteronyssinus (Der p) & Dermatophagoides farinae (Derf) HDM extract (Greer Laboratories Inc.; Der p, Cat#: XPB91D3A2.5, Lot#: 446803; Der f, Cat#:XPB81D3A2.5, Lot#: 435703) by 3 intranasal (i.n.) instillations on 3 consecutive days of 20 pl extract (reconstituted in 0,9% sterile NaCI and diluted in sterile PBS), 10 pl per nostril, containing a total protein content of 2 pg, 1 pg / species. Non-allergic mice received PBS. On days 7, 12 and 19 mice received further i.n. maintenance challenges as described for the sensitization. On days 14, 17 and 21 mice were treated subcutaneously (s.c.) with 200 pl of either sterile 0,9% NaCI (non-allergic, HDM-allergic) or different LNP preparations (Lipid A - D, variation of the ionizable lipid, as in Example 3 above) with 5 pg mRNA / allergen. Finally, on days 29-32, all mice received i.n. challenges with HDM extract with a total protein content of 10 pg total protein, 5 pg / species. Mice were sacrificed on day 35 for further analysis. AIT, allergen-specific immunotherapy; Der f, Dermatophagoides farinae’, Der p, Dermatophagoides pteronyssinus’, HDM, house dust mite; i.n., intranasal; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; NaCI, sodium chloride; PBS, phosphate-buffered saline s.c., subcutaneous.

[0235] Conclusion: Mice are double-sensitized with allergen extract of Dermatophagoides pteronyssinus (Der p) & Dermatophagoides farinae (Der f) and then treated with LNPs containing mRNA encoding for Group 1, 2, and 23 allergens of these species. Note, separate LNPs were produced for each house dust mite species. The results obtained in this model demonstrate efficient treatment of Der p and Der f double-sensitized mice with the 3 major allergens of each species.

[0236] Figure 12 - Cellular Parameters

[0237] Figure 12 (A) shows the quantification of total leukocyte (live CD45+cells) count and the differential cell count of eosinophils (CD11b+CD11c'orlowSiglec-F+Ly6G') in the bronchoalveolar lavage fluid. Cell counts significantly increase after allergic sensitization (HDM-allergic) if compared to non-sensitized mice (non-allergic) reflecting a strong immune cellinfiltration after the induction of allergic airway inflammation. mRNA-based allergenimmunotherapy (s.c.) with differently formulated LNPs (Lipid A - D, each formulated with a different ionizable lipid) is able to reduce the observed cell infiltration. (B) shows the frequency of TH1 (IFN-Y+FOXP3') and TH2 (GATA3+FOXP3‘) within the T-helper cell population (CD45+CD3+CD4+). TH2 are slightly elevated after allergic sensitization and represent a major component of type I allergic diseases (e.g. HDM-allergy) and are associated with a type 2 immune response, while mRNA-based AIT seems to dampen these effects. On the other hand TH1 cells are reduced after sensitization and are significantly increased through mRNA-based AIT. TH1 cells are associated with a type 1 immune response which is generally discussed as counteracting TH2 biased allergic reactions. Statistical analysis was performed on log-transformed data using either Dunnett’s or Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. Non-allergic and HDM-allergic were compared by Welch’s t-test. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergen-specific immunotherapy; CD, cluster of differentiation; FoxP3, forkhead box P3; GATA3, GATA binding protein 3; HDM, house dust mite; IFN-y, interferon y; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; s.c., subcutaneous; Siglec-F, Sialic acid-binding immunoglobulin-like F; TH, T helper cell.

[0238] Conclusion: mRNA-based allergen-immunotherapy (AIT) reduces cell infiltration into the lung with key populations of allergic airway inflammation (eosinophils and TH2) showing a similar trend. Furthermore, all LNP formulations induce potentially beneficial TH1 cell recruitment to the lung.

[0239] Figure 13 - Total Immunoglobulin Levels

[0240] Figure 13 shows the titers of different immunoglobulin classes (total) in the serum. Total IgE levels rise through allergic sensitization and stay elevated throughout the course of the mRNA-based AIT. IgE is another central molecular component of type I hypersensitivity reactions. mRNA-based AIT leads to significant increases in serum titers of total lgG1, lgG2c, and lgG2b. The shift from an IgE dominated to a IgG mediated humoral response is seen as a major hallmark of a successful AIT. Especially high titers of lgG2c are induced in therapeutic groups. Data is displayed on logarithmic scale. Statistical analysis was performed on log-transformed data using Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. Non-allergic and HDM-allergic were compared by Welch’s t-test. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergen-specific immunotherapy; HDM, house dust mite; Ig, immunoglobulin; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid.

[0241] Conclusion: Induced IgE through allergic sensitization remains elevated throughout the treatment course. Independet of LNP formulation, mRNA-based AIT increases serum titers of potentially protective immunoglobulin isotypes lgG1, lgG2c and lgG2b.

[0242] Figure 14 - Allergen-specific lgG1 and lgG2c Titers

[0243] Figure 14 (A) shows the level of allergen-specific lgG1 in the serum, measured as ODA45O values. Measured were lgG1 levels against the group 1 and group 2 HDM allergens of Der p and Derf, as well as Der p 23. Notably, HDM-allergic mice show no induction of allergen-specific lgG1, whereas mRNA-based AIT leads to significant increases of these levels. (B) Similarly, a significant induction of allergen-specific lgG2c was observed after mRNA-based AIT against the group 1 and group 2 HDM allergens of Der p and Der f, as well as Der p 23. Taken together this data shows the potency of the mRNA-based AIT to induce potentially protective IgGs. Statistical analysis was performed using Dunnett’s T3 test for multiple comparisons between the HDM-allergic group and the individual LNP groups. P-values of < .05, < .01, < .001, < .0001 are displayed as *, **, ***, ****, respectively. AIT, allergen-specific immunotherapy; Der p / f, Dermatophagoides pteronyssinus / farinae', HDM, house dust mite; Ig, immunoglobulin; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid; ODA4SO, optical density at 450 nm light wavelength.

[0244] Conclusion: All LNP formulations lead to a robust induction of potentially protective allergen-specific I gG 1 and lgG2c antibody titers.

Claims

CLAIMS1. A RNA construct, comprising or consisting of the following sequences (a), (b), (d) and optionally (c), wherein said sequences are in-frame, preferably in the following order, wherein:a) a RNA sequence encoding for a signal polypeptide is derived from an N-terminal polypeptide fragment of human or murine LAMP-1 (e.g., having a Uniprot accession number: Q8VH34), preferably the polypeptide fragment is at least 15 amino acids long, further preferably the signal polypeptide has at least 75% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2, most preferably said signal polypeptide comprising or consisting of the human SEQ ID NO: 1 and / or the murine SEQ ID NO: 2; b) a RNA sequence encoding for one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 etc., preferably 3 or 6) house dust mite polypeptides, preferably allergens, wherein said polypeptides are selected from the group consisting of (i)-(vi):i) a polypeptide having at least 80% (preferably at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 1 house dust mite polypeptide of SEQ ID NO: 5 (e.g., SEQ ID NO: 5 is Der p 1 sequence within SEQ ID NO: 676, e.g., as in Figure 1 herein);ii) a polypeptide having at least 80% (preferably at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Derf 1 house dust mite polypeptide of SEQ ID NO: 286 (e.g., SEQ ID NO: 286 is Der f 1 sequence within SEQ ID NO: 677, e.g., as in Figure 1 herein);iii) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 2 house dust mite polypeptide of SEQ ID NO: 449 (e.g., SEQ ID NO: 449 is Der p 2 sequence within SEQ ID NO: 678, e.g., as in Figure 1 herein),iiv)a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der f 2 house dust mite polypeptide of SEQ ID NO: 535 (e.g., SEQ ID NO: 535 is Der f 2 sequence within SEQ ID NO: 679, e.g., as in Figure 1 herein),v) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der p 23 house dust mite polypeptide of SEQ ID NO: 621 (e.g., SEQ ID NO: 621 is Der p 23 sequence within SEQ ID NO: 680, e.g., as in Figure 1 herein),vi) a polypeptide having at least 80% (preferably, at least 85%, 90%, 95%, 99% or 100%, further preferably at least 90%) sequence identity to Der f 23 house dust mite polypeptide of SEQ ID NO: 761 (e.g., SEQ ID NO: 761 (DIDHDDDPTTMIDVQTTTVQPSDEFECPTRFGYFADPKDPCKFYICSNWEAIHKSCPGNTRWNEKELTCT) is Der f 23 sequence within SEQ ID NO: 681, e.g., as in Figure 1 herein),c) optionally, a RNA sequence encoding for one or more peptide linkers, preferably said peptide linkers comprising or consisting of the SEQ ID NO: 673;d) a RNA sequence encoding for, preferably in the following order:d’) one or more transmembrane domains, preferably derived from LAMP-1 , LAMP- 2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain and / or Transferrin receptor protein 1; andd”) one or more cytosolic domains, preferably derived from LAMP-1 , LAMP-2, HLA class II histocompatibility antigen gamma chain, HLA class I histocompatibility antigen, A alpha chain, HLA class I histocompatibility antigen, B alpha chain, HLA class I histocompatibility antigen, C alpha chain, and / or Transferrin receptor protein 1;preferably said one or more transmembrane domains and one or more cytosolic domains of (d’)-(d”) have a sequence identity of at least 75% to SEQ ID NO: 674 or SEQ ID NO: 675; further preferably, said one or more transmembrane domains comprising or consisting of the human SEQ ID NO: 674 and / or murine SEQ ID NO: 675.

2. The RNA construct of claim 1, wherein said construct encoding for an enzymatically inactive polypeptide (e.g., according to any construct as shown in Example 4 herein).

3. The RNA construct of any one of the preceding claims, wherein the signal polypeptide is derived from an N-terminal polypeptide fragment of human LAMP-1.

4. The RNA construct of any one of the preceding claims, wherein said RNA construct is suitable for inducing immune tolerance in a subject suffering from house dust mite allergy, suitable for allergen-specific immunotherapy (AIT) and / or for inducing allergen-specific immune tolerance and cross-tolerance against further house dust mite allergens (e.g., referring to the induction of immune tolerance not only to the encoded allergen(s), but also to further allergen species).

5. The RNA construct of any one of the preceding claims, wherein said construct encoding for one or more (preferably 3 or 6, e.g., (i) Der p 1 (SEQ ID NO: 749), Der p 2 (SEQ ID NO: 753) and Der p 23(SEQ ID NO: 757; or (ii) Der f 1 (SEQ ID NO: 751), Der f 2 (SEQ ID NO: 755), Der f 23 (SEQ ID NO: 759)) polypeptide / s comprising or consisting ofpolypeptide / s selected from the group consisting of: SEQ ID NOs: 676-681, 749, 751, 753, 755, 757 and 759 (e.g., as shown in Examples 3-4 herein).

6. The RNA construct of any one of the preceding claims, wherein said RNA molecule is a mRNA molecule, preferably said RNA is a monocistronic or polycistronic mRNA molecule.

7. The RNA construct of any one of the preceding claims, wherein said nucleic acid comprises one or more modified nucleosides, preferably said one or more modified nucleosides are selected from the group consisting of:a) m1lP (1-methylpseudouridine);b) m1acp3lP (1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine);c) ^Pm (2'-0-methylpseudouridine);d) m5D (5-methyldihydrouridine);e) m3^ (3-methylpseudouridine); and / orf) any combination thereof.

8. The RNA construct of any one of the preceding claims, wherein said RNA is engineered or modified to direct the encoded polypeptide to endolysosomal compartments within a cell (e.g., a human cell), preferably, said nucleic acid encodes an endo-lysosomal-targeted polypeptide.

9. An isolated host cell (e.g., isolated recombinant host cell), plurality of said isolated host cells, lipid nanoparticles (LNPs) or polymersomes comprising and / or expressing one or more of the RNA construct / s of any one of the preceding claims.

10. A composition comprising one or more of the RNA construct / s, cell / s, plurality of cells, lipid nanoparticles (LNPs) and / or polymersomes of any one of the preceding claims, preferably said composition is a diagnostic, pharmaceutical composition, immune-therapeutical composition, allergen immunotherapy (AIT) composition, in vitro transcription composition (IVT composition), delivery composition and / or vaccine composition, further preferably said composition is selected from a group consisting: AIT-, IVT- and vaccine composition, most preferably said said composition is a vaccine composition.

11. The composition of claim 10, wherein said composition is a pharmaceutical composition.

12. The RNA construct, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of any one of the preceding claims, for use as a medicament and / or in therapy.1453. The RNA construct, cell, plurality of cells, lipid nanoparticles (LNPs), polymersomes and / or composition of any one of the preceding claims, for use in one or more of the following methods:a) method for treatment, amelioration or prophylaxis of allergy, preferably dust mites allergy;b) method for increasing tolerance to dust mites (preferably in the treatment of house dust mites allergy);c) method for reducing a serum allergen-specific IgE level in a subject (preferably in the treatment of house dust mites allergy); and / ord) any combination of methods as in (a)-(c) (preferably in the treatment of house dust mites allergy).

Images