Development of universal Shigell vaccine based on virulence gen expression.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kyorin University (2022); National Institute of Infectious Diseases (2019)
• Principal Investigator: Mitobe Jiro 杏林大学, 医学部, 教授 (40333364)
• Co-Investigator(Kenkyū-buntansha): 柳原 格 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 免疫部門, 部長 (60314415)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 赤痢菌 / ワクチン / Hfq / RodZ / 免疫染色

Outline of Final Research Achievements

Practical Shigella vaccines are still unbailable because this organism can escape from host immunity by its intracellular propagating life cycle. We found a global regulator of RNA binding protein Hfq is essential for repression of the type III secretion system (T3SS) of Shigella. Deletion of hfq severely affect viability in the host by decrease of stress response but the production of T3SS simultaneously increase by the pleiotropic effect of Hfq. Therefore, we had reported that the deletion mutant of hfq is a potential candidate of Shigella vaccine. In this study, we improve the vaccine strain by adding two mutations that reduce remaining virulence. We found the new vaccine strain still have a protective effect beyond serotypes in animal experiment. We also reported multimer formation of an RNA binding protein RodZ which shows the same virulence phenotype as Hfq in its deletion mutant.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

細菌性赤痢は上下水道が発達した先進国では克服された疾患だが、世界的には発生数と死亡数が共にロタウイルスについで第２位の、いわゆる“顧みられない熱帯病”である。ワクチンが渇望されるが、開発開始から半世紀以上経っても実用化されていない。申請者は赤痢菌群に共通する病原因子を抗原として、血清型に依存しないワクチン改良株を開発し、動物実験レベルでの効果を確認した。また、基礎研究の必要上開発した、細菌の免疫染色法と超解像度顕微鏡で観察する手技を発表論文上で詳細に公開した。