Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment of Type I Allergies

  • Frank Blanco-Pérez
  • Garibald Papp
  • Alexandra Goretzki
  • Tobias Möller
  • Martina Anzaghe
  • Stefan SchülkeEmail author


While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.


Fusion protein Allergen SIT PAMP PRR 



Peptides derived from the major Japanese cedar pollen allergens Cry j 1 and Cry j 2


Ara h 2 peptide


Antigen-presenting cell


Adjuvant system


Active systemic anaphylactic shock


Bronchoalveolar lavage fluid


C-type lectin receptors


Cholera toxin


Catalytic cholera toxin A-subunit


Non-toxic cholera toxin B subunit


Fusion protein consisting of cholera toxin B subunit and peptides derived from the major Japanese cedar pollen allergens Cry j 1 and Cry j 2 (3Crp)


Dendritic cell


Diphtheria toxin


Fungal immunomodulatory protein fve


Forkhead-box-protein 3


Fusion protein consisting of rice gluten subacidic unit and 3Crp


Human serum albumin


House dust mite


Human immunodeficiency virus type 1


Histamine receptor 1/2/4






Intralymphatic immunotherapy


Immunostimulatory oligodeoxynucleotides


Modular antigen translocating


Monophosphoryl lipid A


NOD-like receptors






Fusion protein consisting of the fungal immunomodulatory protein and the major house dust mite allergen Der p 2


Pathogen-associated molecular pattern


Pattern recognition receptor

rCTB-Bet v 1a

Fusion protein consisting of cholera toxin B subunit and Bet v 1a


Fusion protein consisting of flagellin A from Listeria monocytogenes and the major mugwort pollen allergen Art v 1


Fusion protein consisting of flagellin A from Listeria monocytogenes and the major birch pollen allergen Bet v 1


Fusion protein consisting of flagellin A from Listeria monocytogenes and the egg white allergen Ova

rSbpA-Bet v 1

Fusion protein consisting of the S-layer protein SbpA of Bacillus sphaericus CCM 2177 and Bet v 1

rSbsC-Bet v 1

Fusion protein consisting of the S-layer protein of Geobacillus stearothermophilus and Bet v 1

rTAT-Che a 3

Fusion protein consisting of TAT and the main Chenopodium album pollen allergen Che a 3

S-layer protein

Bacterial surface layer proteins


Specific immunotherapy


Fusion protein consisting of the S-layer protein SlpB of Lactobacillus buchneri CD034 and a peptide derived from the major peanut allergen Ara h 2


Trans-activating regulatory protein


Tumor necrosis factor


T helper 1/2/17 response


Toll-like receptors


Regulatory T cell


Tetanus toxoid


Viral protein 1


Fusion protein consisting of a hypoallergenic peptide (P5) of the timothy grass pollen allergen Phl p 1 and VP1



The work was partially supported by the German Research Foundation (DFG).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019

Authors and Affiliations

  1. 1.Vice President’s Research Group: Molecular AllergologyPaul-Ehrlich-InstitutLangenGermany
  2. 2.Product Testing of Immunological BiomedicinesPaul-Ehrlich-InstitutLangenGermany

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