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Concepts and perspectives on peptide-based immunotherapy in allergy

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Abstract

Allergen-specific T cells play a key role in the pathogenesis of allergic diseases through provision of help for allergen-specific B cells and control of inflammatory responses. Allergen immunotherapy using intact allergen proteins (given either subcutaneously or sublingually) is clinically effective and demonstrates enduring efficacy (i. e., disease modifying). However, the requirement for monthly injections or daily sublingual administration (both for 3 years), combined with a high frequency of local and systemic adverse events, results in poor compliance. Targeting allergen-specific T cells with synthetic peptides representing dominant T cell epitopes markedly decreases treatment times (4–8 intradermal injections), reduces adverse events and provides efficacy for at least 2 years. We have developed peptide immunotherapies for allergies triggered by cats, house dust mites, and grass pollen.

Each of these consists of a mixture of seven peptides containing multiple dominant T cell epitopes and each have demonstrated statistically significant improvements in rhinoconjunctivitis symptom scores in controlled allergen challenge facilities. The mechanisms of action appear to involve increased IL-10 production, intra- and inter-molecular suppression, and down-regulation of chemokine pathways. In contrast, treatment does not appear to be associated with deletion of allergen-specific T cells, nor with the induction of allergen-specific IgG (as is seen with conventional whole allergen immunotherapy).

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Abbreviations

AIT:

Allergen immunotherapy

ALLERVAX CAT:

Synthetic cat allergen peptides

Cat-PAD:

Cat peptide antigen desensitization

COP:

Contiguous overlapping peptides

CPT:

Conjunctival provocation test

EEC:

Environmental exposure chamber

EEU:

Environmental Exposure Unit

EPSR:

Early-phase skin responses

GINA:

Global Initiative for Asthma

HDM:

House dust mite

LAR:

Late asthmatic reaction

LPSR:

Late-phase skin response

PBMC:

Peripheral blood mononuclear cell

PD20FEV1:

Provocative dose that induces a 20 % fall in FEV1

PLA2:

Phospholipase A2

SCIT:

Subcutaneous immunotherapy

SLIT:

Sublingual immunotherapy

TRSS:

Total rhinoconjunctivitis symptom score

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Author information

Authors and Affiliations

  1. Division of Clinical Immunology & Allergy, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada

    Elena Tonti & Mark Larché PhD

  2. Division of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada

    Mark Larché PhD

  3. Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, HSC 4H20, 1280 Main Street West, Hamilton, Ontario, L85 4L8, Canada

    Mark Larché PhD

Authors
  1. Elena Tonti
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Correspondence to Mark Larché PhD.

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Conflict of interest

Mark Larché is a co-founder of Circassia Ltd., is a current consultant to the company and a shareholder in Circassia Pharmaceuticals plc. Mark Larché is a consultant to Adiga Life Sciences Inc. Mark Larché has received research development contracts from both Circassia and Adiga Life Sciences. Mark Larché is a named inventor on patents held by Circassia Ltd. In the last 12 months Mark Larché has also acted as a paid consultant to UCB and consults for Aravax Pty. Elena Tonti has received salary support and research grant support from Adiga Life Sciences Inc.

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Tonti E, Larché M. Concepts and perspectives on peptide-based immunotherapy in allergy. Allergo J Int 2016;25:144–53 DOI: 10.1007/s40629-016-0121-5

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Tonti, E., Larché, M. Concepts and perspectives on peptide-based immunotherapy in allergy. Allergo J Int 25, 144–153 (2016). https://doi.org/10.1007/s40629-016-0126-0

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  • DOI: https://doi.org/10.1007/s40629-016-0126-0

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