The development of malaria vaccine platform using baculovirus regulating immune responses

• Project/Area Number: 26860278
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Kanazawa University
• Principal Investigator: IYORI MITSUHIRO 金沢大学, 薬学系, 准教授 (20608351)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: マラリアワクチン / マラリア / ワクチン / バキュロウイルス / 遺伝子組換え原虫

Outline of Final Research Achievements

We have developed the malaria-vaccine platform using several kinds of modified baculovirus such as complement resistant baculovirus, dendritic targeting baculovirus, decoy-receptor expressing baculovirus, cytokine expressing baculovirus and shRNA expressing baculovirus. Among them, complement resistant baculovirus and cytokine expressing baculovirus worked very well in functional analyses. When immunized in mice, these baculovirus induced strong anti-malaria antibody response and conferred high protective efficacy against the infection with transgenic rodent malaria.

Research Products

• [Journal Article] Development of a Plasmodium berghei transgenic parasite expressing the full-length Plasmodium vivax circumsporozoite VK247 protein for testing vaccine efficacy in a murine model (2016)
  • Author(s): Masanori Mizutani, Shinya Fukumoto, Adam Patrice Soubeiga, Akira Soga, Mitsuhiro Iyori Shigeto Yoshida
  • Journal Title: Malaria J Volume: 15 Issue: 1 Pages: 251-258
  • DOI: 10.1186/s12936-016-1297-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro. (2015)
  • Author(s): Sala KA, Nishiura H, Upton LM, Zakutansky SE, Delves MJ, Iyori M, Mizutani M, Sinden RE, Yoshida S, Blagborough AM.
  • Journal Title: Vaccine Volume: 33 Issue: 3 Pages: 437-45
  • DOI: 10.1016/j.vaccine.2014.11.038
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The crystal structure of the active domain of Anopheles anti-platelet protein, a powerful anti-coagulant, in complex with an antibody. (2014)
  • Author(s): Sugiyama, K., Iyori, M., Sawaguchi, A., Akashi, S., Tame, J.R.H., Park, S.-Y., Yoshida, S.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 23 Pages: 16303-16312
  • DOI: 10.1074/jbc.m114.564526
  • Peer Reviewed / Open Access
• [Journal Article] Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites (2014)
  • Author(s): Mizutani, M. Iyori, M. Blagborough, A. M. Fukumoto, S. Funatsu, T. Sinden, R. E. Yoshida, S.
  • Journal Title: Infect Immun Volume: 82 Issue: 10 Pages: 4348-4357
  • DOI: 10.1128/iai.02040-14
  • Peer Reviewed / Open Access
• [Presentation] Plasmodium falciparum CSP vaccine based on a heterologous adenoviru-sprime and baculovirus-boost immunization regimen confers sterile protection against transgenic P.berghei sporozoite challenge (2017)
  • Author(s): Kunitaka Yoshida, Mitsuhiro Iyori, Ahmed M. Salman, Pawan Dulal, Shahid M. Khan, Chris J. Janse, Sumi Biswas, Masaharu Tokoro, Andrew M. Blagborough, Adrian V.S. Hill, Shigeto Yoshida
  • Organizer: The U.S.‐Japan Cooperative Medical Sciences Program Presents the 19th International Conference on Emerging Infectious Diseases (EID)
  • Place of Presentation: Novotel Ambassador Seoul Gangnam
  • Year and Date: 2017-02-07
  • Int'l Joint Research
• [Presentation] Enhanced protective efficacy of a P. falciparum malaria vaccine using a heterologous prime-boost immunization with a baculoviral vaccine and ChAd63 expressing PfCSP against challenge with a transgenic P. berghei sporozoites (2016)
  • Author(s): Kunitaka Yoshida, Ahmed M. Salman, Pawan Dulal, Shahid M. Khan, Chris J. Janse, Sumi Biswas, Masaharu Tokoro, Mitsuhiro Iyori, Andrew M. Blagborough, Adrian V. S. Hill, Shigeto Yoshida
  • Organizer: ASTMH 65th Annual Meeting
  • Place of Presentation: Atlanta Marriott Marquis
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Vectored PfCSP Vaccines based on Baculovirus Dual Expression System and AdHu5 induce Strong Protective Efficacy against Transgenic Plasmodium berghei (2016)
  • Author(s): Mitsuhiro Iyori, Andrew M. Blagborough, Sota Ogata, Hidesato Nishiura, Miako Sakaguchi, Masanori Mizutani, Takahiko Tamura, Kento Genshi, Satoshi Shimada, Daisuke S. Yamamoto, Hiroyuki Matsuoka and Shigeto Yoshida
  • Organizer: ASTMH 65th Annual Meeting
  • Place of Presentation: Atlanta Marriott Marquis
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] A hybrid Plasmodium falciparum malaria vaccine based on adenovirus-prime and baculovirus-boost immunization regimen (2016)
  • Author(s): Kunitaka Yoshida, Mitsuhiro Iyori, Ahmed M. Salman, Pawan Dulal, Shahid M. Khan, Chris J. Janse, Sumi Biswas, Masaharu Tokoro, Andrew M. Blagborough, Adrian V.S. Hill, Shigeto Yoshida
  • Organizer: 第57回日本熱帯医学会大会
  • Place of Presentation: 学術総合センター（東京）
  • Year and Date: 2016-11-05
• [Presentation] アデノウイルスベクターとバキュロウイルスベクターを用いた新規ワクチンプラットフォームによる熱帯熱マラリアワクチンの開発 (2016)
  • Author(s): 吉田邦嵩, Ahmed M. Salman, Pawan Dulal, Shahid M. Khan, Chris J. Janse, Sumi Biswas, 所正治, 伊従光洋, Andrew M. Blagborough, Adrian V.S. Hill, 吉田栄人
  • Organizer: 第72回日本寄生虫学会西日本支部大会
  • Place of Presentation: 岐阜大学サテライトキャンパス
  • Year and Date: 2016-10-15
• [Presentation] A hybrid Plasmodium falciparum malaria vaccine based on adenovirus-prime and baculovirus-boost immunization regimen. (2016)
  • Author(s): Kunitaka Yoshida, Ahmed M. Salman, Pawan Dulal, Shahid M. Khan, Chris J. Janse, Sumi Biswas, Masaharu Tokoro, Mitsuhiro Iyori, Andrew M. Blagborough, Adrian V. S. Hill, Shigeto Yoshida
  • Organizer: 第14回松山国際学術シンポジウム
  • Place of Presentation: 愛媛大学
  • Year and Date: 2016-09-15
  • Int'l Joint Research
• [Presentation] Antibody response against the Anopheles salivary gland protein reflects Plasmodium falciparum infection during the rainy season in Indonesia. (2016)
  • Author(s): 伊従 光洋，藤吉 里紗，Syafruddin Din，吉田 栄人
  • Organizer: 第85回日本寄生虫学会
  • Place of Presentation: 宮崎市民プラザ（宮崎）
  • Year and Date: 2016-03-20
• [Presentation] Baculovirus-induced innate immunity confers 100% protection against sporozoite challenge in a mouse model. (2016)
  • Author(s): Emran Talha B.，天野 隆之，Fitri Amelia，Asrar Alam，松岡 裕之，小川 良平，伊 従 光洋，吉田 栄人
  • Organizer: 第85回日本寄生虫学会
  • Place of Presentation: 宮崎市民プラザ（宮崎）
  • Year and Date: 2016-03-19
• [Presentation] 蚊唾液タンパクの能動免疫によるネズミマラリア原虫に対する感染防御効果 (2016)
  • Author(s): 伊従 光洋、吉田 栄人
  • Organizer: 第68回日本衛生動物学会
  • Place of Presentation: 栃木県総合文化センター
• [Presentation] 超高齢社会に求められる新しいコンセプトの抗血小板薬の開発研究 (2016)
  • Author(s): 伊従光洋
  • Organizer: 日本薬学会北陸支部第128回例会
  • Place of Presentation: 北陸大学
  • Invited
• [Presentation] マラリア媒介蚊の唾液タンパクを基盤とした創薬研究 (2015)
  • Author(s): 伊従光洋
  • Organizer: 平成27年度 第3回生体応答科学研究セミナー
  • Place of Presentation: 弘前大学（青森）
  • Year and Date: 2015-12-18
  • Invited
• [Presentation] 次世代マラリアワクチンの開発と創薬研究 (2015)
  • Author(s): 伊従光洋
  • Organizer: 平成27年度 第２回大学院活性化講演会
  • Place of Presentation: 弘前大学（青森）
  • Year and Date: 2015-12-17
  • Invited
• [Presentation] Differential antibody response to the Anopheles stephensi AAPP and Plasmodium antigens in individuals naturally exposed to bites of afrotropical malaria vectors. (2015)
  • Author(s): Mitsuhiro Iyori, Risa Fujiyoshi, Din Syafrudin, Shigeto Yoshida
  • Organizer: 64th ASTMH Annual meeting
  • Place of Presentation: Philadelphia Marriott Downtown (USA)
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] 高速原子間力顕微鏡を用いたハマダラカ由来唾液タンパク観察の試み (2015)
  • Author(s): 伊従光洋，中山隆弘，藤吉里紗，吉田栄人
  • Organizer: 第33回北陸病害動物研究会
  • Place of Presentation: 金沢大学（石川）
  • Year and Date: 2015-06-13
• [Presentation] 抗蚊唾液抗体価を用いたマラリア疫学調査の新規評価法の開発 -インドネシア介入 試験時の季節的変動- (2015)
  • Author(s): 伊従光洋、藤吉里紗、Din Syafruddin、吉田栄人
  • Organizer: 第67回日本衛生動物学会大会
  • Place of Presentation: 金沢大学（石川）
  • Year and Date: 2015-03-27 – 2015-03-28
• [Presentation] マラリア媒介蚊唾液由来AAPP の抗血小板凝集阻害活性の機能解析 (2015)
  • Author(s): 伊従光洋
  • Organizer: 第67回日本衛生動物学会大会
  • Place of Presentation: 金沢大学（石川）
  • Year and Date: 2015-03-27 – 2015-03-28
  • Invited
• [Presentation] バキュロウイルスを基盤とした新型マラリアワクチンの開発研究 (2015)
  • Author(s): 伊従光洋
  • Organizer: 第23回病害動物の生理分子生物談話会
  • Place of Presentation: 金沢大学（石川）
  • Year and Date: 2015-03-27
  • Invited
• [Presentation] 蚊唾液タンパクに対する抗体価を用いた新規マラリア疫学調査法の開発 (2015)
  • Author(s): 伊従光洋、藤吉里紗、Din Syafruddin、吉田栄人
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学（東京）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] 抗蚊唾液抗体価を用いたマラリア疫学調査の新規評価法の開発 -インドネシア介入試験前のベースライン抗体価の調査- (2014)
  • Author(s): 伊従光洋、藤吉里紗、Din Syafruddin、吉田栄人
  • Organizer: 第69回日本衛生動物学会西日本支部大会
  • Place of Presentation: 愛知医科大学（愛知）
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] 補体抵抗性因子発現型バキュロウイルスベクターを用いたマラリアワクチンに関する研究 (2014)
  • Author(s): 西浦秀里、緒方壮大、松岡祐之、山本大介、坂口美亜子、伊従光洋、水谷征法、田村隆彦、吉田栄人
  • Organizer: 第70回日本寄生虫学会西日本支部大会
  • Place of Presentation: 兵庫医療大学（神戸）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] バキュロウイルスベクターを用いた三日熱マラリアマルチステージワクチンの開発研究 (2014)
  • Author(s): 伊従光洋、水谷征法、舟津知宏、Blagborough AM、福本晋也、Sinden RE、吉田栄人
  • Organizer: 第70回日本寄生虫学会西日本支部大会
  • Place of Presentation: 兵庫医療大学（神戸）
  • Year and Date: 2014-10-18 – 2014-10-19
• [Presentation] 感染防御-伝播阻止の両機能を搭載した三日熱マラリア２価ワクチンの開発 (2014)
  • Author(s): 水谷征法、舟津知宏、伊従光洋、AM. Blagborough、福本晋也、RE.Sinden、吉田栄人
  • Organizer: 第22回分子寄生虫学ワークショップ/第12回分子寄生虫・マラリア研究フォーラム合同大会
  • Place of Presentation: 帯広畜産大学原虫病研究センターPKホール（北海道）
  • Year and Date: 2014-08-31 – 2014-09-03
• [Presentation] インドネシア人血清を用いた蚊唾液タンパクに対する抗体価評価法の開発 (2014)
  • Author(s): 伊従光洋、藤吉里紗、舟津知宏、澤口明日香、Din Syafruddin、吉田栄人
  • Organizer: 第32回北陸病害動物研究会
  • Place of Presentation: 丸三製薬（富山）
  • Year and Date: 2014-06-21