Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles

Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting s...

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Bibliographic Details
Published in:Biomaterials 2023-12, Vol.303, p.122381-122381, Article 122381
Main Authors: Li, Shunyi, Toriumi, Hiroki, Takahashi, Daisuke, Kamasaki, Tomoko, Fujioka, Yoichiro, Nagatoishi, Satoru, Li, Jinting, Liu, Yiwei, Hosokawa, Takanatsu, Tsumoto, Kouhei, Ohba, Yusuke, Katayama, Yoshiki, Murakami, Daisuke, Hase, Koji, Mori, Takeshi
Format: Article
Language:English
Subjects:
Allergens
anaphylaxis
Animals
antigen presentation
asthma
biocompatible materials
crosslinking
Dendritic Cells
Desensitization, Immunologic
disulfide bonds
Glutaral
glutaraldehyde
Humans
Hypersensitivity
immunotherapy
Immunotherapy - methods
Mannans
Mice
nanoparticles
Nanoparticles - chemistry
Ovalbumin
patient compliance
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Summary:Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting strategies to treat allergies such as glutaraldehyde crosslinked antigen to mannoprotein (MAN) have been established. However, glutaraldehyde crosslinking may reduce the antigen presentation efficiency of DCs. To overcome this, we developed a MAN-coated ovalbumin (OVA) nanoparticle (MDO), which uses intermolecular disulfide bond to crosslink OVA and MAN. MDO effectively targeted DCs resulting in tolerogenic DCs, and promoted higher antigen presentation efficiency by DCs compared with OVA or glutaraldehyde crosslinked nanoparticles. In vitro and in vivo experiments showed that DCs exposed to MDO induced T cells. Moreover, MDO had low reactivity with anti-OVA antibodies and did not induce anaphylaxis in allergic mice, demonstrating its high safety profile. In a mouse model of allergic asthma, MDO had significant preventative and therapeutic effects when administered orally or subcutaneously. Therefore, MDO represents a promising new approach for the efficient and safe treatment of allergies.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2023.122381