Modulating shrimp tropomyosin-mediated allergy: Hypoallergen DNA vaccines induce regulatory T cells to reduce hypersensitivity in mouse model

Christine Y.Y. Wai, Nicki Y.H. Leung, Patrick S.C. Leung, Ka Hou Chu

Research output: Contribution to journalArticle

Abstract

Shellfish allergy is one of the most common food allergies, with tropomyosin as the major cross-reactive allergen. However, no allergen-specific immunotherapy is clinically available. Recently, we designed two shrimp hypoallergens MEM49 and MED171. This study aimed to examine and compare the efficacy of the MEM49- and MED171-based DNA vaccines (pMEM49 and pMED171) in modulating shrimp allergy in a murine model of shrimp tropomyosin sensitivity. Intradermal immunization of BALB/c mice with pMEM49 or pMED171 effectively down-modulated allergic symptoms, tropomyosin-specific IgE levels, intestinal Th2 cytokines expression, and inflammatory cell infiltration. Both pMEM49 and pMED171 increased the frequency of regulatory T cells, but to a greater extent by pMED171 with upregulation of gut-homing molecules integrin-α4β7. The functionality of the pMED171-induced Treg cells was further illustrated by anti-CD25-mediated depletion of Treg cells and the adoptive transfer of CD4+CD25+Foxp3+Treg cells. Collectively, the data demonstrate that intradermal administration of pMED171 leads to the priming, activation, and migration of dermal dendritic cells which subsequently induce Treg cells, both locally and systemically, to downregulate the allergic responses to tropomyosin. This study is the first to demonstrate the potency of hypoallergen-encoding DNA vaccines as a therapeutic strategy for human shellfish allergy via the vigorous induction of functional Treg cells.

Original languageEnglish (US)
Article number4656
JournalInternational journal of molecular sciences
Volume20
Issue number18
DOIs
StatePublished - Sep 2 2019

Fingerprint

vaccines
Allergies
Tropomyosin
DNA Vaccines
T-cells
Regulatory T-Lymphocytes
mice
Hypersensitivity
deoxyribonucleic acid
Allergens
Shellfish
cells
shellfish
Immunization
Infiltration
Integrins
Immunoglobulin E
Immunologic Desensitization
homing
Langerhans Cells

Keywords

  • Adoptive transfer
  • Food allergy
  • Hypoallergen
  • Immunotherapy
  • Tolerance induction
  • Vaccination

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Modulating shrimp tropomyosin-mediated allergy : Hypoallergen DNA vaccines induce regulatory T cells to reduce hypersensitivity in mouse model. / Wai, Christine Y.Y.; Leung, Nicki Y.H.; Leung, Patrick S.C.; Chu, Ka Hou.

In: International journal of molecular sciences, Vol. 20, No. 18, 4656, 02.09.2019.

Research output: Contribution to journalArticle

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