Study of lipsomal vaccine entrapping MHC-binding peptides for production of secretory IgA against Shiga-like toxin B subunit

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: KUROHANE KOHTA 静岡県立大学, 薬学部, 講師 (90333525)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: IgA / ワクチン / 免疫学 / リポソーム / ベロ毒素

Outline of Final Research Achievements

B-subunit of Shiga-like toxin (Stx1B) has been demonstrated to be a poor immunogenicity. To augments the immunogenicity of Stx1B, major histocompatibility complex class II bind peptides, including T cell epitopes, and Stx1B were liposomalized. Mice were given Stx1B-liposomes via nasal cavity. As a result, lipsomalization of Stx1B efficiently augmented the immunogenicity of Stx1B in the mucosal immune systems. Moreover, secretory IgA (SIgA) genes were obtained from anti-Stx1B SIgA producing hybridoma. These genes were transfected into CHO-K1 cells to obtain anti-Stx1B SIgA in vitro. It was able to obtain anti-Stx1B SIgA has neutralizing activity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

粘膜免疫の効果的な誘導、抗原特異的IgA 抗体産生ハイブリドーマの作製、抗体を構成する遺伝子を用いて分泌型IgAを構築することが可能になれば、粘膜に投与可能な治療用抗体としての分泌型IgAの研究が大きく発展する。本研究では、病原細菌由来の毒素を抗原として用いることで、臨床応用可能な治療用抗体の作製が可能となる点にも特徴がある。本研究の概念を応用すれば、抗原性に関わらず、粘膜免疫を効果的に賦活化できる経粘膜ワクチンの開発、粘膜に適用可能な治療用分泌型IgAの開発につながり、感染症予防に大きく寄与すると思われる。