A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells

He Wen; Litian Qu; Yu Zhang; Beilei Xu; Shiqi Ling; Xiaochun Liu; Yang Luo; Da Huo; Wei Li; Xu Yao

doi:10.1159/000512872

A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells

Int Arch Allergy Immunol. 2021;182(9):777-787. doi: 10.1159/000512872. Epub 2021 Jul 21.

Authors

He Wen^{1

2}, Litian Qu³, Yu Zhang^{1

2}, Beilei Xu^{1

2}, Shiqi Ling^{1

2}, Xiaochun Liu^{1

2}, Yang Luo^{1

2}, Da Huo⁴, Wei Li⁵, Xu Yao^{1

2}

Affiliations

¹ Department of Allergy and Rheumatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
² Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
³ Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁴ Department of Pharmacy, Nanjing Medical University, Nanjing, China.
⁵ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China, liweiderma@fudan.edu.cn.

PMID: 34289474
DOI: 10.1159/000512872

Abstract

Background: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen.

Objectives: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT.

Methods: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed.

Results: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization.

Conclusions: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.

Keywords: Allergen; Allergen-specific immunotherapy; Dendritic cells; Immune tolerance; Mannan; Polylactic-co-glycolic acid; Treg cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allergens / administration & dosage
Allergens / immunology*
Animals
Dendritic Cells / immunology*
Desensitization, Immunologic
Hypersensitivity / immunology
Hypersensitivity / therapy
Immune Tolerance
Immunization
Mannans / immunology*
Mice
Nanoparticles*
Polylactic Acid-Polyglycolic Acid Copolymer*
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / metabolism
Vaccines / immunology*

Substances

Allergens
Mannans
Vaccines
Polylactic Acid-Polyglycolic Acid Copolymer