Development of a live attenuated monkey malaria vaccine with enhanced antigenicity

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19566
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Nagasaki University
• Principal Investigator: KANEKO Osamu 長崎大学, 熱帯医学研究所, 教授 (50325370)
• Co-Investigator(Kenkyū-buntansha): 川合 覚 獨協医科大学, 医学部, 教授 (70275733)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: マラリア / 赤血球侵入 / ワクチン / サル / 遺伝子改変

Outline of Final Research Achievements

Monkey malaria parasite Plasmodium knowlesi causes zoonotic human malaria in the natural environment in Southeast Asia. Because classical methods to control human malaria cannot efficiently control this zoonosis, we believe that vaccine is crucial to combat P. knowlesi. In this study, we aimed to establish methods to control the parasite ability to invade erythrocytes and to increase the parasite antigenicity, which would be used to develop a live attenuated erythrocyte stage P. knowlesi malaria vaccine for human usage. To increase the antigenicity, we tried to disrupt SETvs gene locus, which would result to express all repertoires of antigens on the erythrocyte surface, whose expression was otherwise suppressed. However, we could not obtain transgenic parasites so far. On the other hand, we were able to obtain transgenic P. knowlesi whose ability to invade human erythrocytes was increased by introducing a Plasmodium falciparum ligand recognizing mature human erythrocytes.

Free Research Field

基礎医学・寄生虫学（含衛生動物学）

Academic Significance and Societal Importance of the Research Achievements

本研究により、二日熱マラリア原虫の赤血球期生ワクチン創出のための技術基盤の一部が整った。また、ヨーロッパなどでは、サル赤血球の入手が困難なため、１年もの年月をかけてヒト赤血球を用いた培養に適応させた二日熱マラリア原虫株が研究に用いられているが、簡便にヒト赤血球で培養ができる株は一株のみである。本研究で開発した技術を応用することで、様々な二日熱マラリア原虫株を、簡便にヒト赤血球を用いた培養に適応させることができるため、高い波及効果を持つと考える。