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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
Review
  • 114 Downloads

Abstract

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.

Keywords

Fusion protein Allergen SIT PAMP PRR 

Abbreviations

3Crp

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

AH3a42

Ara h 2 peptide

APC

Antigen-presenting cell

AS

Adjuvant system

ASAS

Active systemic anaphylactic shock

BALF

Bronchoalveolar lavage fluid

CLR

C-type lectin receptors

CT

Cholera toxin

CTA

Catalytic cholera toxin A-subunit

CTB

Non-toxic cholera toxin B subunit

CTB-3Crp

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)

DC

Dendritic cell

DT

Diphtheria toxin

FIP-fve

Fungal immunomodulatory protein fve

Foxp3

Forkhead-box-protein 3

GLU-3Crp

Fusion protein consisting of rice gluten subacidic unit and 3Crp

HAS

Human serum albumin

HDM

House dust mite

HIV-1

Human immunodeficiency virus type 1

HR1/2/4

Histamine receptor 1/2/4

IFN

Interferon

IL

Interleukin

ILIT

Intralymphatic immunotherapy

ISS–ODN

Immunostimulatory oligodeoxynucleotides

MAT

Modular antigen translocating

MPLA

Monophosphoryl lipid A

NLRs

NOD-like receptors

ODN

Oligodeoxynucleotides

Ova

Ovalbumin

OsDp2Fve

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

PAMP

Pathogen-associated molecular pattern

PRR

Pattern recognition receptor

rCTB-Bet v 1a

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

rFlaA:Artv1

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

rFlaA:Betv1

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

rFlaA:Ova

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

SIT

Specific immunotherapy

SlpB-AH3a42

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

TAT

Trans-activating regulatory protein

TNF

Tumor necrosis factor

Th1/2/17

T helper 1/2/17 response

TLRs

Toll-like receptors

Treg

Regulatory T cell

TT

Tetanus toxoid

VP1

Viral protein 1

VP1-2xP5

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

Notes

Acknowledgements

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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