Screening of the RBC receptor molecules for malaria merozoite invasion based on wheat germ cell free system

• Project/Area Number: 25460517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Ehime University
• Principal Investigator: Takashima Eizo 愛媛大学, プロテオサイエンスセンター, 准教授 (50366762)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マラリア / 赤血球 / マラリア原虫 / メロゾイト / 原虫リガンド / 侵入 / 分子寄生虫学 / 生化学 / ワクチン / 原虫 / プロテインアレイ

Outline of Final Research Achievements

Merozoite invasion of malaria parasite is attributed with the parasite erythrocyte binding antigens (EBA). In this study, we attempted to screen for identification of the receptor molecules on the surface of the host RBC for the EBAs. By means of comprehensive immuno-precipitation with more than 200 polyclonal antibodies, we identified the molecule interacting with GPI-anchored micronemal antigen (GAMA), a blood stage vaccine candidate. We named the molecule GAMA association protein (GAAP). Biacore analysis revealed that Kd value of the interaction was 2.5 nM. We also identified the GAAP interacting domain in GAMA which has about 100 amino acid residues.

Research Products

• [Int'l Joint Research] Mahidol University(Thailand)
• [Int'l Joint Research] Kangwon National University(韓国)
• [Journal Article] An Evolution-Based Screen for Genetic Differentiation between Anopheles Sister Taxa Enriches for Detection of Functional Immune Factors. (2015)
  • Author(s): Mitri C, Bischoff E, Takashima E, Williams M, Eiglmeier K, Pain A, Guelbeogo WM, Gneme A, Brito-Fravallo E, Holm I, Lavazec C, Sagnon N, Baxter RH, Riehle MM, Vernick KD
  • Journal Title: PLoS Pathog Volume: 11 Issue: 12 Pages: 1-24
  • DOI: 10.1371/journal.ppat.1005306
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunoprofiling of the tryptophan-rich antigen family in Plasmodium vivax (2015)
  • Author(s): Wang B, Lu F, Cheng Y, Chen JH, Jeon HY, Ha KS, Cao J, Nyunt MH, Han JH, Lee SK, Kyaw MP, Sattabongkot J, Takashima E, Tsuboi T, Han ET
  • Journal Title: Infect Immun Volume: 83 Issue: 8 Pages: 3083-3095
  • DOI: 10.1128/iai.03067-14
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Application of wheat germ cell-free protein expression system for novel malaria vaccine candidate discovery (2014)
  • Author(s): Arumugam TU, Ito D, Takashima E, Tachibana M, Ishino T, Torii M, Tsuboi T
  • Journal Title: Expert Review of Vaccines Volume: 13 Issue: 1 Pages: 75-85
  • DOI: 10.1586/14760584.2014.861747
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Plasmodium vivax merozoite surface protein 1 paralog is a novel erythrocyte-binding ligand of P. vivax. (2013)
  • Author(s): Cheng Y, Wang Y, Ito D, Kong DH, Ha KS, Chen JH, Lu F, Li J, Wang B, Takashima E, Sattabongkot J, Tsuboi T, Han ET.
  • Journal Title: Infection and Immunity Volume: 81 Issue: 5 Pages: 1585-1595
  • DOI: 10.1128/iai.01117-12
  • Peer Reviewed
• [Journal Article] RALP1 is a rhoptry neck erythrocyte-binding protein of Plasmodium falciparum merozoites and a potential blood-stage vaccine candidate antigen (2013)
  • Author(s): Ito D, Hasegawa T, Miura K, Yamasaki T, Arumugam TU, Thongkukiatkul A, Takeo S, Takashima E, Sattabongkot J, Han ET, Long CA, Torii M, *Tsuboi
  • Journal Title: Infect Immun Volume: 81 Issue: 11 Pages: 4290-4298
  • DOI: 10.1128/iai.00690-13
  • Peer Reviewed
• [Journal Article] Functional comparison of Plasmodium falciparum transmission-blocking vaccine candidates by the standard membrane-feeding assay (2013)
  • Author(s): Miura K, Takashima E, Tsuboi T. (他9名)
  • Journal Title: Infect Immun Volume: 81(12) Issue: 12 Pages: 4377-82
  • DOI: 10.1128/iai.01056-13
  • Peer Reviewed
• [Journal Article] A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut. (2013)
  • Author(s): Mathias DK, Pastrana-Mena R, Ranucci E, Ferruti P, de Beaumont C, Ortega C, Staples GO, Zaia J, Takashima E, Tsuboi T, Verotta L, Dinglasan RR
  • Journal Title: PLoS Pathogens Volume: 9 Issue: 11 Pages: e1003757-e1003757
  • DOI: 10.1371/journal.ppat.1003757
  • Peer Reviewed
• [Presentation] 赤血球侵入メカニズムの解明に向けた熱帯熱マラリア原虫メロゾイト分子間相互作用 (2016)
  • Author(s): 高島英造、今川瑞希、長岡ひかる、坪井敬文
  • Organizer: 第８５回 日本寄生虫学会大会
  • Place of Presentation: 宮崎市民プラザ、宮崎県、宮崎市
  • Year and Date: 2016-03-19
• [Presentation] Profiling of antibody responses against Plasmodium falciparum protein array in Ugandan children for identification of novel blood-stage vaccine candidates. (2015)
  • Author(s): Kanoi BN, Takashima E, Morita M, Ntege EH, Balikagala B, Palacpac NMQ, Egwang TG, Horii T, Tsuboi T.
  • Organizer: ASTMH 64th annual meeting
  • Place of Presentation: Philadelphia Marriott Downtown, Philadelphia, USA
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] Genome-wide immunoscreening of antibodies responsible for Plasmodium falciparum growth inhibitory activity of Malian adult IgG. (2015)
  • Author(s): Morita M, Takashima E, Kanoi BN, Miura K, Long CA, Tsuboi T.
  • Organizer: ASTMH 64th annual meeting
  • Place of Presentation: Philadelphia Marriott Downtown, Philadelphia, USA
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] Identification of Plasmodium falciparum PfMAS170 as novel blood-stage malaria vaccine candidate (2015)
  • Author(s): Takashima E, Sasaoka C, Sakamoto H, Ito D, Takeo S, Sattabongkot J, Tsuboi T.
  • Organizer: 25th Annual Molecular Parasitology/Vector Biology Symposium
  • Place of Presentation: University of Georgia, Athens, USA
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Presentation] Preclinical prioritization of blood-stage malaria vaccine candidates of Plasmodium falciparum using wheat germ cell-free system. (2013)
  • Author(s): Tsuboi T, Yamasaki T, Arumugam TU, Ito D, Hasegawa T, Takashima E, Miura K, Long CA, Cowman AF, Torii M.
  • Organizer: ASTMH 62nd annual meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Targeting sexual stage malaria parasites with transmission-blocking compounds in the mosquito midgut. (2013)
  • Author(s): Mathias DK, Pastrana-Mena R, Ranucci E, Ferruti P, Takashima E, Tsuboi T, Borg NA, Verotta L, Dinglasan RR.
  • Organizer: ASTMH 62nd annual meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] Shinzawa N, Takashima E, Katsube R, Nozaki M, Tachibana M, Kato A, Thongkukiatkul A, Tsuboi T, Torii M, Ishino T (2013)
  • Author(s): Plasmodium Alveolin 5 is essential for the normal formation of inner membrane complex of ookinetes.
  • Organizer: ASTMH 62nd annual meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] RALP1, a rhoptry-neck, erythrocyte-binding protein of Plasmodium falciparum merozoites, is a novel vaccine candidate antigen. (2013)
  • Author(s): Ito D, Hasegawa T, Yamasaki T, Arumugam TU, Miura K, Thongkukiatkul A, Takeo S, Long CA, Sattabongkot J, Han ET, Takashima E, Torii M, Tsuboi T.
  • Organizer: ASTMH 62nd annual meeting
  • Place of Presentation: Washington DC, USA
• [Remarks] 愛媛大学 プロテオサイエンスセンター マラリア研究部門
  • URL: http://www.pros.ehime-u.ac.jp/malaria/
• [Remarks] 愛媛大学PROSプロテオサイエンスセンター マラリア研究部門
  • URL: http://www.pros.ehime-u.ac.jp/malaria/
• [Remarks] 愛媛大学 プロテオサイエンスセンター
  • URL: http://www.pros.ehime-u.ac.jp/