2018 Fiscal Year Final Research Report

Understanding the mechanisms of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in mucosal adjuvanticity

Research Project

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Project/Area Number	17K16068
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory organ internal medicine
Research Institution	National Institutes of Biomedical Innovation, Health and Nutrition
Principal Investigator	Kusakabe Takato 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所ワクチン・アジュバント研究センター, プロジェクト研究員 (20794035)
Project Period (FY)	2017-04-01 – 2019-03-31
Keywords	アジュバント / 粘膜アジュバント / シクロデキストリン / ワクチン / DAMP / IL-33 / 経鼻 / 作用機序
Outline of Final Research Achievements	Vaccinology has focused on non-living vaccines, which are more stable and safety than live-attenuated vaccines but often show limited immunogenicity. Vaccine adjuvants are traditionally used to augment and modulate the immunogenicity of vaccines. We previously reported that hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used pharmaceutical excipient to improve solubility, can be used effectively as an adjuvant for influenza vaccine in both subcutaneous and intranasal administration. However, the molecular mechanisms of adjuvanticity of HP-β-CD hasn't been investigated in detail. In this study, we observed HP-β-CD to release of IL-33 but not elevated in other vaccine adjuvants. Furthermore, our data suggest that IL-33/ST2 signaling is responsible for the adjuvant effect of HP-β-CD by intranasal administration. Our study suggests that the understanding of administration route and tissue-specific immune responses are critical for the design of unique vaccine adjuvants.
Free Research Field	ワクチン学・粘膜免疫学
Academic Significance and Societal Importance of the Research Achievements	肺や鼻腔局所の粘膜免疫に関して、局所の細胞がどのような働きをしているのかについては未だ不明な点が多い. そのような背景において、本研究では、粘膜アジュバントのメカニズムの一つとしてIL-33が関与していることを見出した. 本発見はIL-33を介したアジュバント物質としては初めてとなる. また、IL-33は近年アレルギーの分野で注目を浴びているサイトカインであるが、本研究では感染防御効果に寄与するという利点があるということでIL-33の役割の多様性を見出した.