Development of a live attenuated monkey malaria vaccine with enhanced antigenicity

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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.

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。

Research Products

• [Int'l Joint Research] ロンドン大学衛生熱帯医学大学院(英国)
• [Int'l Joint Research] 南フロリダ大学(米国)
• [Int'l Joint Research] 国立江原大学校(韓国)
• [Int'l Joint Research] London Sch Hyg Trop Med(英国)
• [Int'l Joint Research] Kangwon National University(韓国)
• [Int'l Joint Research] London Sch Hyg Trop Med(United Kingdom)
• [Int'l Joint Research] Kangwon National University(韓国)
• [Journal Article] Development of an effective alternative model for in vivo hypnozoite-induced relapse infections: a Japanese macaque (Macaca fuscata) model experimentally infected with Plasmodium cynomolgi (2020)
  • Author(s): Kawai S, Annoura T, Araki T, Shiogama Y, Shogo S, Sato MO, Kaneko O, Yasutomi Y, Chigusa Y.
  • Journal Title: Parasitology International Volume: 76 Pages: 102096-102096
  • DOI: 10.1016/j.parint.2020.102096
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to P. knowlesi. (2020)
  • Author(s): Muh F, Kim N, Nyunt MH, Firdaus ER, Han JH, Hoque MR, Lee SK, Park JH, Moon RW, Lau YL, Kaneko O, Han HT
  • Journal Title: PLoS Neglected Tropical Diseases Volume: 14 Issue: 6 Pages: e0008323-e0008323
  • DOI: 10.1371/journal.pntd.0008323
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan's clefts in the infected erythrocyte (2018)
  • Author(s): Kumi Asare Kwame、Sakaguchi Miako、Byaruhanga Lucky Amuza、Asada Masahito、Miyazaki Shinya、Katakai Yuko、Kawai Satoru、Song Chihong、Murata Kazuyoshi、Yahata Kazuhide、Kaneko Osamu
  • Journal Title: Parasitology International Volume: 印刷中 Issue: 4 Pages: 481-492
  • DOI: 10.1016/j.parint.2018.04.005
  • Peer Reviewed / Open Access
• [Journal Article] Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi (2018)
  • Author(s): Muh Fauzi、Ahmed Md Atique、Han Jin-Hee、Nyunt Myat Htut、Lee Seong-Kyun、Lau Yee Ling、Kaneko Osamu、Han Eun-Taek
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5781-5781
  • DOI: 10.1038/s41598-018-23728-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] An exogenously expressed Plasmodium falciparum ligand significantly improved Plasmodium knowlesi ability to invade human erythrocytes (2019)
  • Author(s): Asare KK, Lucky AB, Kaneko M, Xangsayarath P, Katakai Y, Kawai S, Yahata K, Adams JH, Kaneko O.
  • Organizer: The American Society of Tropical Medicine and Hygiene, 68th annual meeting
  • Int'l Joint Research
• [Presentation] An exogenously expressed Plasmodium falciparum EBA-175 enables Plasmodium knowlesi to quickly adapt to human erythrocytes in vitro. (2019)
  • Author(s): Kaneko O, Asare KK, Lucky AB, Kaneko M, Xangsayarath P, Katakai Y, Kawai S, Yahata K, Adams JH.
  • Organizer: 第60回日本熱帯医学会大会
• [Presentation] An exogenously expressed Plasmodium falciparum ligand enables Plasmodium knowlesi to adapt to human erythrocytes in vitro. (2019)
  • Author(s): Asare KK, Lucky AB, Kaneko M, Xangsayarath P, Katakai Y, Kawai S, Yahata K, Adams JH, Kaneko O.
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] Identification of the ligand responsible for the cytoadhesion of Plasmodium knowlesi-infected red blood cells. (2019)
  • Author(s): Chuang H, Lucky AB, Yamagishi J, Katakai Y, Kawai S, Kaneko O, Sakaguchi M.
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] Cytoadhesion of Plasmodium knowlesi-infected red blood cells to human endothelial cells (2019)
  • Author(s): Sakaguchi M, Lucky AB, Yamaghishi J, Katakai Y, Kawai S, Kaneko O
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program: Parasitic Diseases and Immunology Panel Meeting
  • Int'l Joint Research
• [Presentation] Identification of the ligand responsible for the cytoadhesion of Plasmodium knowlesi-infected red blood cells (2018)
  • Author(s): Sakaguchi M, Lucky AB, Yamagishi J, Katakai Y, Kawai S, Kaneko O
  • Organizer: 14th International Congress of Parasitology
  • Int'l Joint Research
• [Presentation] Amorphous structure connects a nascent Golgi-like Sinton Mulligan’s clefts to Plasmodium knowlesi infected erythrocyte membrane (2018)
  • Author(s): Asare KK, Sakaguchi M, Lucky AB, Asada M, Miyazaki S, Katakai Y, Kawai S, Song C, Murata K, Yahata K, Kaneko O
  • Organizer: The 17th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan's clefts in the infected erythrocyte (2018)
  • Author(s): Asare KK, Sakaguchi M, Lucky AB, Asada M, Miyazaki S, Katakai Y, Kawai S, Song C, Murata K, Yahata K, Kaneko O
  • Organizer: The American Society of Tropical Medicine and Hygiene, 67th annual meeting
  • Int'l Joint Research
• [Presentation] Amorphous structure connects a nascent Golgi-like Sinton Mulligans clefts to Plasmodium knowlesi-infected erythrocyte membrane (2018)
  • Author(s): Kaneko O, Asare KK, Sakaguchi M, Lucky AB, Asada M, Miyazaki S, Katakai Y, Kawai S, Song C, Murata K, Yahata K
  • Organizer: 第59回日本熱帯医学会大会
• [Presentation] マラリア原虫の寄生赤血球への分子輸送 (2018)
  • Author(s): 金子修
  • Organizer: 第59回日本熱帯医学会大会
  • Invited
• [Presentation] Tether-like structures connect Sinton-Mulligan’s clefts and erythrocyte membrane in Plasmodium knowlesi-infected erythrocyte (2017)
  • Author(s): Asare KK, Lucky AB, Sakaguchi M, Asada M, Miyazaki S, Katakai Y, Kawai S, Song C, Murata K, Yahata K, Kaneko O.
  • Organizer: The 13th Nagasaki-Singapore Medical Symposium / Leading Program International Symposium 2017