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

Shunyi Li; Hiroki Toriumi; Daisuke Takahashi; Tomoko Kamasaki; Yoichiro Fujioka; Satoru Nagatoishi; Jinting Li; Yiwei Liu; Takanatsu Hosokawa; Kouhei Tsumoto; Yusuke Ohba; Yoshiki Katayama; Daisuke Murakami; Koji Hase; Takeshi Mori

doi:10.1016/j.biomaterials.2023.122381

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

Biomaterials. 2023 Dec:303:122381. doi: 10.1016/j.biomaterials.2023.122381. Epub 2023 Oct 31.

Authors

Affiliations

¹ Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, 819-0395, Japan.
² Division of Biochemistry, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, 105-8512, Japan.
³ Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, 105-8512, Japan.
⁴ Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
⁵ The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan.
⁶ Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, 819-0395, Japan.
⁷ Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, 819-0395, Japan; Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, 819-0395, Japan; Center for Future Chemistry, Kyushu University, Fukuoka, 819-0395, Japan; International Research Center for Molecular Systems, Kyushu University, Fukuoka, 819-0395, Japan; Centre for Advanced Medicine Innovation, Kyushu University, Fukuoka, 812-8582, Japan; Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, 32023, Taiwan. Electronic address: katayama.yoshiki.958@m.kyushu-u.ac.jp.
⁸ Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: murakami.daisuke.181@m.kyushu-u.ac.jp.
⁹ Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, 105-8512, Japan; The Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Kanayagawa, Fukushima, 960-1296, Japan; International Research and Development Centre for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, 108-8639, Japan. Electronic address: hase-kj@pha.keio.ac.jp.
¹⁰ Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, 819-0395, Japan; Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, 819-0395, Japan; Center for Future Chemistry, Kyushu University, Fukuoka, 819-0395, Japan. Electronic address: mori.takeshi.880@m.kyushu-u.ac.jp.

PMID: 37935073
DOI: 10.1016/j.biomaterials.2023.122381

Abstract

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_reg 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.

Keywords: Allergen-specific immunotherapy; Dendritic cells; Mannan-coated allergen nanoparticle; Mannoprotein; Tolerance.

Publication types

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

MeSH terms

Allergens
Animals
Dendritic Cells
Desensitization, Immunologic
Glutaral
Humans
Hypersensitivity*
Immunotherapy / methods
Mannans
Mice
Nanoparticles* / chemistry
Ovalbumin

Substances

Mannans
Glutaral
Allergens
Ovalbumin