Discovery of novel blood-stage malaria vaccine candidates based on the molecular function

• Project/Area Number: 26253026
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Ehime University
• Principal Investigator: TSUBOI Takafumi 愛媛大学, プロテオサイエンスセンター, 教授 (00188616)
• Co-Investigator(Kenkyū-buntansha): 高島 英造 愛媛大学, プロテオサイエンスセンター, 准教授 (50366762)
• Research Collaborator: MORITA Masayuki 愛媛大学, プロテオサイエンスセンター, 研究員 (60709632)
• Project Period (FY): 2014-06-27 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥40,820,000 (Direct Cost: ¥31,400,000、Indirect Cost: ¥9,420,000); Fiscal Year 2016: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2015: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2014: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
• Keywords: マラリア / 赤血球期ワクチン / コムギ無細胞法 / コンビネーションワクチン

Outline of Final Research Achievements

In order to identify novel blood-stage malaria vaccine candidates of Plasmodium falciparum, we have expressed 142 putative merozoite specific recombinant proteins. Among them, 34 bounded to the RBC surface. We then analyzed extent of polymorphism in four promising RBC-binding proteins, PfRipr, PfRALP1, PfGAMA, and PfMSPDBL1 using clinical isolates from a region of high malaria transmission in Uganda. PfRipr gene was most highly conserved among the four genes investigated. In addition, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies and performed functional growth inhibition assay (GIA) on the heterologous FVO parasite strain. The GIA activity of anti-PfRipr antibody was highest among the four antibodies even on the polymorphic FVO parasite strain. Thus, PfRipr is regarded as a promising blood-stage malaria vaccine against P. falciparum.

Research Products

• [Int'l Joint Research] Burnet institute/Walter & Elisa Hall Institute(オーストラリア)
• [Int'l Joint Research] Med Biotech Laboratories(ウガンダ)
• [Int'l Joint Research] Mahidol University(Thailand)
• [Int'l Joint Research] Kangwon National University(Korea)
• [Journal Article] Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes. (2016)
  • Author(s): Bargieri DY, Thiberge S, Tay CL, Carey AF, Rantz A, Hischen F, Lorthiois A, Straschil U, Singh P, Singh S, Triglia T, Tsuboi T, Cowman A, Chitnis C, Alano P, Baum J, Pradel G, Lavazec C, Menard R.
  • Journal Title: Cell Host Microbe. Volume: 20 Pages: 618-630
  • DOI: 10.1016/j.chom.2016.10.015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate. (2016)
  • Author(s): Ntege EH, Arisue N, Ito D, Hasegawa T, Palacpac NM, Egwang TG, Horii T, Takashima E, Tsuboi T.
  • Journal Title: Vaccine Volume: 34 Pages: 5612-5622
  • DOI: 10.1016/j.vaccine.2016.09.028
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status. (2016)
  • Author(s): Cheng Y, Lu F, Wang B, Li J, Han JH, Ito D, Kong DH, Jiang L, Wu J, Ha KS, Takashima E, Sattabongkot J, Cao J, Nyunt MH, Kyaw MP, Desai SA, Miller LH, Tsuboi T, Han ET.
  • Journal Title: Sci Rep. Volume: 6 Pages: 35581-35581
  • DOI: 10.1038/srep35581
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. (2016)
  • Author(s): Weaver R, Reiling L, Feng G, Drew DR, Mueller I, Siba PM, Tsuboi T, Richards JS, Fowkes FJ, Beeson JG.
  • Journal Title: Sci Rep. Volume: 6 Pages: 33094-33094
  • DOI: 10.1038/srep33094
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antibody responses to Plasmodium falciparum and Plasmodium vivax blood-stage and sporozoite antigens in the postpartum period. (2016)
  • Author(s): McLean AR, Boel ME, McGready R, Ataide R, Drew D, Tsuboi T, Beeson JG, Nosten F, Simpson JA, Fowkes FJ.
  • Journal Title: Sci Rep. Volume: 6 Pages: 32159-32159
  • DOI: 10.1038/srep32159
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization. (2015)
  • Author(s): Tachibana M, Suwanabun N, Kaneko O, Iriko H, Otsuki H, Sattabongkot J, Kaneko A, Herrera S, Torii M, Tsuboi T
  • Journal Title: Vaccine Volume: 33 Pages: 1901-1908
  • DOI: 10.1016/j.vaccine.2015.03.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rodent malaria lactate dehydrogenase assay provides a high throughput solution for in vivo vaccine studies (2015)
  • Author(s): Otsuki H, Yokouchi Y, Iyoku N, Tachibana M, Tsuboi T, Torii M
  • Journal Title: Parasitol Int Volume: 64 Pages: 60-63
  • DOI: 10.1016/j.parint.2015.02.001
  • Peer Reviewed / Acknowledgement Compliant
• [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 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 Rev Vaccines Volume: 13 Pages: 75-85
  • DOI: 10.1586/14760584.2014.861747
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tricomponent complex loaded with a mosquito-stage antigen of malaria parasite induces potent transmission-blocking immunity. (2014)
  • Author(s): Arakawa T, Tsuboi T, Sattabongkot J, Sakao K, Torii M, Miyata T
  • Journal Title: Clinical Vaccine and Immunology Volume: 21 Pages: 561-569
  • DOI: 10.1128/cvi.00053-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Profiling the humoral immune responses to Plasmodium vivax infection and identification of candidate immunogenic rhoptry-associated membrane antigen (RAMA) (2014)
  • Author(s): Lu F, Li J, Wang B, Cheng Y, Kong DH, Cui L, Ha KS, Sattabongkot J, Tsuboi T, Han ET
  • Journal Title: J Proteomics Volume: 102 Pages: 66-82
  • DOI: 10.1016/j.jprot.2014.02.029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunogenicity and antigenicity of Plasmodium vivax merozoite surface protein 10 (2014)
  • Author(s): Cheng Y, Wang B, Sattabongkot J, Lim CS, Tsuboi T, Han ET
  • Journal Title: Parasitol Res Volume: 113 Pages: 2559-2568
  • DOI: 10.1007/s00436-014-3907-8
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Post-genome malaria vaccine research. (2017)
  • Author(s): Tsuboi T
  • Organizer: Japan-Brazil Malaria Research Workshop: fostering new partnerships
  • Place of Presentation: Sao Paulo, Brazil
  • Year and Date: 2017-03-15
  • Int'l Joint Research / Invited
• [Presentation] Post-genome malaria vaccine candidate discovery by wheat germ cell-free system (2016)
  • Author(s): Tsuboi T
  • Organizer: Joint International Tropical Medicine Meeting 2016
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2016-12-07
  • Int'l Joint Research / Invited
• [Presentation] ポストゲノム生化学研究：マラリアワクチン研究の突破口 (2016)
  • Author(s): 坪井敬文、高島英造、森田将之
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター、宮城県仙台市
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] Reverse vaccinology approach: Postgenome malaria blood-stage vaccine candidate discovery. (2016)
  • Author(s): Tsuboi T, Ntege EH, Takashima E, Morita M, Ito D, Cowman A.
  • Organizer: International Congress for Tropical Medicine and Malaria 2016
  • Place of Presentation: Brisbane, Australia
  • Year and Date: 2016-09-18
  • Int'l Joint Research
• [Presentation] Approaches to malaria vaccine development. (2016)
  • Author(s): Tsuboi T
  • Organizer: Workshop on Tools for Malaria Eradication
  • Place of Presentation: RIKEN Yokohama Campus, Yokohama, Kanagawa, Japan
  • Year and Date: 2016-06-06
  • Int'l Joint Research / Invited
• [Presentation] ポストゲノムマラリアワクチン研究は宿主寄生体関係の総体的理解につながる (2015)
  • Author(s): 坪井敬文
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会年会 合同大会
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Pre-erythrocytic vaccines for malaria elimination (2015)
  • Author(s): Tsuboi T
  • Organizer: Malaria R&D in a Time of Global Partnerships
  • Place of Presentation: 東京大学、東京都
  • Year and Date: 2015-06-26
  • Int'l Joint Research / Invited
• [Presentation] an integrated approach to tackling malaria in Uganda with special reference to novel malaria vaccine candidate discovery (2015)
  • Author(s): Tsuboi T, Kanoi BN, Egwang TG, Horii T
  • Organizer: E-JUST 2nd International Conference on Innovative Engineering
  • Place of Presentation: Bibliotheca Alexandria, Alexandria, Egypt
  • Year and Date: 2015-05-19
  • Int'l Joint Research / Invited
• [Presentation] WGCFS: an innovative technology for post-genome malaria vaccine research (2015)
  • Author(s): 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 / Invited
• [Presentation] Wheat germ cell-free protein synthesis system (WGCFS): a breakthrough for the post-genome malaria research (2014)
  • Author(s): Tsuboi T
  • Organizer: Seminar at the Department of Parasite and Insect Vectors, Institut Pasteur
  • Place of Presentation: Paris, France
  • Year and Date: 2014-12-18
  • Invited
• [Presentation] Wheat germ cell-free protein synthesis system: an innovative technology for post-genome malaria vaccine candidate discovery (2014)
  • Author(s): Tsuboi T
  • Organizer: Seminar at the Laboratory of Malaria and Vector Research, NIAID, NIH
  • Place of Presentation: Rockville, USA
  • Year and Date: 2014-11-07
  • Invited
• [Presentation] Antibodies against a Plasmodium falciparum rhoptry neck protein PfRON12 inhibit merozoite invasion into erythrocytes (2014)
  • Author(s): Ito D, Takashima E, Hatano S, Yamasaki T, Hasegawa T, Miura K, Thongkukiatkul A, Long CA, Sattabongkot J, Torii M, Tsuboi T
  • Organizer: The 63rd annual meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2014-11-02 – 2014-11-06
• [Presentation] Identification of the novel transmission-blocking vaccine target expressing on the surface of male gametes (2014)
  • Author(s): Tachibana M, Torii M, Sudo M, Tsuboi T, Ishino T
  • Organizer: The 63rd annual meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2014-11-02 – 2014-11-06
• [Presentation] Immunoscreening of the target proteins contributing to growth inhibitory activity of human IgG against Plasmodium falciparum (2014)
  • Author(s): Morita M, Takashima E, Kanoi BN, Miura K, Tsuboi T
  • Organizer: The 63rd annual meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2014-11-02 – 2014-11-06
• [Presentation] Rhoptry proteins are involved in sporozoite invasion of the salivary gland (2014)
  • Author(s): Nozaki M, Ishino T, Tokunaga N, Tsuboi T, Torii M
  • Organizer: The 63rd annual meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2014-11-02 – 2014-11-06
• [Presentation] Global Health Innovation through Partnership (2014)
  • Author(s): Tsuboi T
  • Organizer: 第55回日本熱帯医学会大会・第29回日本国際保健医療学会学術大会合同大会
  • Place of Presentation: 東京女子医科大学、東京都
  • Year and Date: 2014-11-01 – 2014-11-03
  • Invited
• [Presentation] Characterization of Plasmodium falciparum MAS170 as novel malaria blood-stage vaccine candidate (2014)
  • Author(s): Sasaoka C, Sakamoto H, Ito D, Takeo S, Sattabongkot J, Takashima E, Tsuboi T
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 奈良春日野国際フォーラム、奈良市、奈良県
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Wheat germ cell-free protein synthesis system: an innovative technology for post-genome malaria vaccine candidate discovery (2014)
  • Author(s): 坪井敬文
  • Organizer: 第157回日本獣医学会学術集会、日本獣医寄生虫学会国際シンポジウム
  • Place of Presentation: 北海道大学、札幌市、北海道
  • Year and Date: 2014-09-09 – 2014-09-12
  • Invited
• [Presentation] Wheat germ cell-free protein synthesis system (WGCFS): a breakthrough for the post-genome vivax malaria research (2014)
  • Author(s): Tsuboi T, Takashima E, Ito D, Feng Lu, Cheng Y, Han ET
  • Organizer: 13th International Congress of Parasitology
  • Place of Presentation: Mexico City, Mexico
  • Year and Date: 2014-08-10 – 2014-08-15
  • Invited
• [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/