Construction and application of recombinant protein of Rickettsia

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K19866
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Society medicine, Nursing, and related fields
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Satoh Masaaki 国立感染症研究所, ウイルス第一部, 主任研究官 (30442966)
• Project Period (FY): 2017-06-30 – 2021-03-31
• Keywords: 日本紅斑熱 / Rickettsia japonica / モデル動物 / 感染実験

Outline of Final Research Achievements

Japanese spotted fever (JSF) is a tick-borne infectious disease cause by Rickettsia japonica. In this study, we established the method for definition of infectious dose of R. japonica. Using this method, we measured the minimum inhibitory concentration of several antibiotics against R. japonica. This result was published the Journal of Infection and Chemotherapy. Next, we attempted to establish the murine model of JSF. By inoculation of 1E6 PFU of viable R. japonica, C3H/HeN and BALB/c mice survived for 28 days. Weight loss of C3H/HeN mice were significant compared with those of BALB/c mice. Specific sera against R. japonica were detected. And Pathology of R. japonica infection was indicated by histological analysis. DNAs of R. japonica were detected in blood, brain, lung, liver, and spleen of 1E6 PFU of viable R. japonica-inoculated C3H/HeN mice. From these results we propose that C3H/HeN mice inoculated 1E6 PFU of viable R. japonica are available murine model of JSF.

Free Research Field

感染症　ウイルス　ワクチン

Academic Significance and Societal Importance of the Research Achievements

R. japonicaの感染価測定の系を確立したことで、今後ワクチンの効果を測定するための50％致死量を決定に応用できる。また、日本紅斑熱のモデル動物の確立を提唱することで、今後、未だに不明瞭な部分がある日本紅斑熱の病態進行メカニズムやそれに伴う宿主の免疫反応の解明といった基礎研究で、またモデル動物を用いて薬剤試験を行うことで、日本紅斑熱治療における適正な薬剤使用についてのガイドラインを確立することに寄与できる。ワクチンおよび組換えタンパク質のようなサブユニットワクチンの効果測定といった日本紅斑熱の予防に向けた臨床への応用ににつながることが期待できた。