Novel nano paticle vaccine | Biogenesis and medical application of outer membrane vesicles

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22644
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Nakao Ryoma 国立感染症研究所, 細菌第一部, 主任研究官 (10370959)
• Co-Investigator(Kenkyū-buntansha): 泉福 英信 国立感染症研究所, 細菌第一部, 室長 (20250186) ; 平山 悟 新潟大学, 医歯学系, 助教 (70778555)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 外膜小胞 / ワクチン

Outline of Final Research Achievements

In the present study, we investigated a mechanism of outer membrane vesicle (OMV) production by Porphyromonas gingivalis (Pg) and Escherichia coli (Ec). First, we found that Pg has two different modes of the OMV production: one is a mode occurring during normal bacterial growth, and the other is a way of OMV production induced by antimicrobials. We suggest that Pg OMVs induced by antimicrobials may be involved in deprivation of two outer membrane transporter proteins, RagA and RagB in the bactericidal process. Subsequently, we identified a cryptic plasmid gene, kil, involved in the production of OMVs in Ec. In addition, we discovered a breakthrough strategy in mass production of OMVs with low endotoxin content, by adding glycine to culture broth. Furthermore, in vivo vaccine studies using OMVs of two periodontopathic bacteria, Pg and Aggregatibacter actinomycetemcomitans (Aa), revealed both the safety and efficacy of this divalent OMV vaccine via intranasal route.

Free Research Field

細菌学・分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られたOMVs産生機構の理解に基づき、OMVsワクチンの生産効率に寄与する技術の開発応用が期待される。また実際に、マウスモデルでの歯周病原細菌由来OMVs経鼻ワクチンの効果と安全性が明らかにされた。今後は、歯周病のみならず、様々な感染症に対するワクチン開発研究においても、OMVsが利用できる可能性が示された。