Malaria vaccine development based on multifunctional hybrid vaccine platform

• Project/Area Number: 15H04723
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Kanazawa University
• Principal Investigator: Yoshida Shigeto 金沢大学, 薬学系, 教授 (10296121)
• Co-Investigator(Kenkyū-buntansha): 伊従 光洋 金沢大学, 薬学系, 准教授 (20608351) ; 福本 晋也 帯広畜産大学, 原虫病研究センター, 准教授 (50376422) ; 小川 良平 富山大学, 大学院医学薬学研究部(医学), 准教授 (60334736) ; 田村 隆彦 金沢大学, 薬学系, 助教 (00434035) ; 松岡 裕之 自治医科大学, 医学部, 教授 (10173816)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: マラリア / ワクチン / 感染防御 / スポロゾイト / バキュロウイルス / ハマダラカ

Outline of Final Research Achievements

We have generated baculovirus- and adenovirus-based malaria vaccines expressing Plasmodium circumsporozoite protein (PfCSP) or PfCSP-Pfs25 fusino protein. Immunization of mice with these viral-vectored vaccines induced high anti-PfCSP and Pfs25 antibody titers and cellular immune responses. These results clearly demonstrated that our vaccines possesses multifunctional effects on induction of both humoral and cellular immune responses. We successfully achieved sterile protective efficacy of our vaccines against sporozoite challenge. Moreover, heterologous prime-boost immunization regime using baculovirus- and adenovirus-PfCSP-Pfs25 elicited 99% transmission blocking activity. The present study shows great potential of our vaccines as next-generating malaria vaccines.

Research Products

• [Int'l Joint Research] University of Oxford/Imperial College London(United Kingdom)
• [Int'l Joint Research] Leiden University(オランダ)
• [Int'l Joint Research] Imperial College London(英国)
• [Int'l Joint Research] University of Oxford/Imperial College London(United Kingdom)
• [Journal Article] Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model. (2018)
  • Author(s): Yoshida K, Iyori M, Blagborough AM, Salman AM, Dulal P, Sala KA, Yamamoto DS, Khan SM, Janse CJ, Biswas S, Yoshii T, Yusuf Y, Tokoro M, Hill AVS, Yoshida S
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 3896-3896
  • DOI: 10.1038/s41598-018-21369-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Protective efficacy of an IL-12-expressing baculoviral malaria vaccine (2017)
  • Author(s): Iyori M.、Blagborough A. M.、Sala K. A.、Nishiura H.、Takagi K.、Yoshida S.
  • Journal Title: Parasite Immunology Volume: 39 Issue: 12
  • DOI: 10.1111/pim.12498
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice. (2017)
  • Author(s): Iyori M, Yamamoto DS, Sakaguchi M, Mizutani M, Ogata S, Nishiura H, Tamura T, Matsuoka H, Yoshida S
  • Journal Title: Malaria Journal Volume: 16 Issue: 1 Pages: 390-390
  • DOI: 10.1186/s12936-017-2039-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] マラリア PfCSP タンパクのワクチン抗原としての免疫原性および感染防御効果の検討 (2018)
  • Author(s): Fitri AMELIA. 伊従 光洋. 玄師 健人. 尾上 裕太郎. Talha Bin EMRAN. Yenni YUSUF. 吉田 栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] コラーゲン誘導性血小板凝集阻害活性を有するハマダラカ唾液タンパク AAPP の機能を喪失すると吸血 行動が制限される (2018)
  • Author(s): Ashekul ISLAM. 伊従 光洋. 山本 大介. Talha Bin EMRAN. 都野 展子. 山口 莉理夏. Henrique SILVEIRA. 吉田 栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] アデノウイルスとアデノ随伴ウイルス用いたheterologous prime-boost immunization によるマラリアワクチンの開発研究 (2018)
  • Author(s): Yenni YUSUF. 吉田 邦嵩. 伊従 光洋. 吉井 達也. 橋爪 洋樹. 島田 聡. 水上 浩明. 山本 大介. 福本晋也. 吉田 栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] ウイルスベクターと組換えタンパクを組み合わせたマラリアワクチンの開発研究 (2018)
  • Author(s): 大塚 広夢. 島田 聡. 伊従 光洋. 吉田 邦嵩. 吉田栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] アデノ随伴ウイルスベクターを用いたマラリアワクチン開発研究 (2018)
  • Author(s): 吉井 達也. 伊従 光洋. 吉田 邦嵩. 島田 聡. Yenni YUSUF. 水上 浩明. 吉田 栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] 組換えワクシニアウイルス LC16m8Δ のマラリアワクチン効果 (2018)
  • Author(s): 堀 直人. 伊従 光洋. 吉田 邦嵩. Talha Bin EMRAN. 島田 聡. 志田 壽利. 吉田 栄人.
  • Organizer: 日本薬学会第138年会
• [Presentation] ウイルスベクターを基盤としたマラリアワクチンの開発 (2018)
  • Author(s): 伊従光洋
  • Organizer: 日本薬学会第138年会
• [Presentation] Vectored PfCSP Vaccines based on Baculovirus Dual Expression System and AdHu5 induce Strong Protective Efficacy against Transgenic Plasmodium berghei (2017)
  • 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: アメリカ アトランタ
  • Year and Date: 2017-11-13
  • Int'l Joint Research
• [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)
• [Presentation] P. falciparum multistage viral-vectored vaccines effective for both sporozoite protection and transmission blocking (2017)
  • Author(s): Asrar Alam、Mitsuhiro Iyori、Kunitaka Yoshida、Yenni Yusuf、Katarzyna A Sala、Andrew M Blagborough、Eizo Takashima、Takafumi Tsuboi、Shigeto Yoshida
  • Organizer: 第86回日本寄生虫学会
• [Presentation] Protective efficacy of viral vectored Plasmodium falciparum malaria vaccines by the prime-boost immunization regimen (2017)
  • Author(s): 伊従 光洋 、吉田 邦嵩、Salman Ahmed 、Dulal Pawan 、Khan Shahid 、 Biswas Sumi、所 正治、Andrew Blagborough 、Adrian Hill、吉田 栄人
  • Organizer: 第86回日本寄生虫学会
• [Presentation] Transgene mediated inhibition of collagen-induced platelet aggregation by Anopheline Anti-Platelet Protein, regulates probing time and blood feeding success in malaria vector mosquito Anopheles stephensi (2017)
  • Author(s): Islam Ashekul, Talha Bin Emran, Daisuke Yamamoto, Mitsuhiro Iyori, Fitri Amelia, Yenni Yusuf, Nobuko Tuno, Yoshida Shigeto
  • Organizer: 第35回北陸病害動物研究会
• [Presentation] Development of viral-vectored Plasmodium vivax circumsporozoite vaccines and its evaluation system in a murine model (2017)
  • Author(s): Yenni Yusuf, Mitsuhiro Iyori, Masanori Mizutani, Asrar Alam,Fitri Amelia, Talha bin Emran, Ashekul Islam, Shigeto Yoshida
  • Organizer: 第73回日本寄生虫学会西日本支部大会
• [Presentation] Evaluation of the immunogenicity and vaccine efficacy of recombinant truncated protein PfCSP region in a murine malaria model (2017)
  • Author(s): Fitri Amelia, Mitsuhiro Iyori, Kento Genshi, Yutaro Onoue,Talha Bin Emran, Yenni Yusuf, Ashekul Islam, Shigeto Yoshida
  • Organizer: 第73回日本寄生虫学会西日本支部大会
• [Presentation] Transgene mediated inhibition of collagen-induced platelet aggregation by Anopheline Anti-Platelet Protein, regulates probing time and blood feeding success in malaria vector mosquito Anopheles stephensi (2017)
  • Author(s): Ashekul Islam, Mitsuhiro Iyori, Daisuke Yamamoto, Nobuko Tuno, Talha Bin Emran, Fitri Amelia, Yenni Yusuf, Henrique Silveira, Yoshida Shigeto
  • Organizer: 第73回日本寄生虫学会西日本支部大会
• [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: アメリカ アトランタ
  • 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: 一橋大学
  • 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
  • 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): 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] 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: 栃木県宇都宮市
  • Year and Date: 2016-04-15
• [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回日本寄生虫学会大会
  • Place of Presentation: 宮崎市民プラザ
  • Year and Date: 2016-03-19
• [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
  • Year and Date: 2015-12-17
• [Presentation] 組織標的性を持つ遺伝子導入ベクターとしての次世代バキュロウイルスの開発 (2015)
  • Author(s): 田村隆彦、川井悠輔、川端千明、松下俊介、坂口美亜子、吉田栄人
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-04
• [Presentation] 補体抵抗性バキュロウイルスの作成とその評価 (2015)
  • Author(s): 川井悠輔，田村隆彦，吉田栄人
  • Organizer: 日本薬学会北陸支部第127回例会
  • Place of Presentation: 富山大学
  • Year and Date: 2015-11-15
• [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
  • Place of Presentation: Philadelphia Marriott Downtown
  • Year and Date: 2015-10-25