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Development of next-generation vaccine strains against neosporosis and their application for vector based on protozoan parasite

Research Project

Project/Area Number 20K21359
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

Nishikawa Yoshifumi  帯広畜産大学, 原虫病研究センター, 教授 (90431395)

Co-Investigator(Kenkyū-buntansha) 渡邉 謙一  帯広畜産大学, 畜産学部, 准教授 (10761702)
Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords原虫 / ネオスポラ / ワクチン / ベクター / ガン / 遺伝子編集
Outline of Research at the Start

本研究では家畜の流産の原因原虫であるネオスポラに対するワクチン開発のために、我々が確立した遺伝子編集技術を基盤として、原虫独自の代謝経路と感染伝搬能力を欠損させた次世代のワクチン株を作出する。また細胞内寄生原虫は強力な自然免疫を誘導することが可能であり、その潜在的な免疫活性化能に着目すればネオスポラのワクチン株をベクターとして応用することが可能である。従って、異種抗原遺伝子(トキソプラズマ、マラリア原虫、癌細胞)を導入したベクターワクチン株を作製し、獣医寄生虫学研究から難治性疾患の制圧戦略に向けた新たな医薬バイオテクノロジー分野の創出を目指す挑戦的な研究を実施する。

Outline of Final Research Achievements

Although the progress in immunology has led to the development of various vaccines against viruses and bacteria, the development of vaccines against protozoan diseases has been extremely difficult. Recent advances in gene editing technology have facilitated the introduction and disruption of genes in various organisms, and in the field of parasite research, it has become possible to reduce the virulence of the parasites by gene disruption. In this study, based on our gene editing technology, we generated a next-generation Neospora vaccine strain that lacks the ability to transmit infection, and confirmed its protective effect against infection with Neospora and its therapeutic effect against cancer. It is expected that the attenuated strain will be used to control intractable parasitic diseases and to develop a cancer vaccine.

Academic Significance and Societal Importance of the Research Achievements

近年、様々なサブユニットワクチン開発が行われ、ウイルスベクターを中心にヒトでの臨床開発が進められている。しかしながら、ウイルスベクターの安全性が懸念されている。一方、ネオスポラはヒトでの免疫誘導能は保持するが病原性・感染性は極めて低く、細胞ゲノムへの組込みリスクや体外排出は認められない。従って、ネオスポラのベクター化の試みが癌などの難治性疾患の制圧戦略に向けた新たな研究分野の創出へ寄与する可能性が期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (53 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (10 results) Journal Article (20 results) (of which Int'l Joint Research: 15 results,  Peer Reviewed: 20 results,  Open Access: 14 results) Presentation (16 results) (of which Int'l Joint Research: 1 results) Book (2 results) Remarks (5 results)

  • [Int'l Joint Research] Mahidol University(タイ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Sylhet Agricultural University/Chattogram University(バングラデシュ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] South Valley University/Sohag University(エジプト)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Sylhet Agricultural University(バングラデシュ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Mahidol University,/Kasetsart University,/Mahanakorn University of Technology(タイ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] South Valley University/Mansoura University(エジプト)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Chattogram University(バングラデシュ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] South Valley University/Mansoura University(エジプト)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] National Taiwan University(その他の国・地域)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Cebu Technological University(フィリピン)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Evaluation of Immunodiagnostic Performances of Neospora caninum Peroxiredoxin 2 (NcPrx2), Microneme 4 (NcMIC4), and Surface Antigen 1 (NcSAG1) Recombinant Proteins for Bovine Neosporosis2024

    • Author(s)
      Udonsom Ruenruetai、Adisakwattana Poom、Popruk Supaluk、Reamtong Onrapak、Jirapattharasate Charoonluk、Thiangtrongjit Tipparat、Rerkyusuke Sarinya、Chanlun Aran、Hasan Tanjila、Kotepui Manas、Siri Sukhontha、Nishikawa Yoshifumi、Mahittikorn Aongart
    • Journal Title

      Animals

      Volume: 14 Issue: 4 Pages: 531-531

    • DOI

      10.3390/ani14040531

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neospora caninum surface antigen 1 is a major determinant of the pathogenesis of neosporosis in nonpregnant and pregnant mice2024

    • Author(s)
      Abdelbaky Hanan H.、Rahman Md. Masudur、Shimoda Naomi、Chen Yu、Hasan Tanjila、Ushio Nanako、Nishikawa Yoshifumi
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 1334447-1334447

    • DOI

      10.3389/fmicb.2023.1334447

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Involvement of chemokine receptor CXCR3 in the defense mechanism against Neospora caninum infection in C57BL/6 mice.2023

    • Author(s)
      Abdelbaky HH, Mitsuhashi S, Watanabe K, Ushio N, Miyakawa M, Furuoka H, Nishikawa Y
    • Journal Title

      Front Microbiol.

      Volume: 13 Pages: 1045106-1045106

    • DOI

      10.3389/fmicb.2022.1045106

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoproteomics to identify species-specific antigens in Neospora caninum recognised by infected bovine sera.2022

    • Author(s)
      Udonsom R, Reamtong O, Adisakwattana P, Popruk S, Jirapattharasate C, Nishikawa Y, Inpankaew T, Toompong J, Kotepui M, Mahittikorn A
    • Journal Title

      Parasite

      Volume: 29 Pages: 60-60

    • DOI

      10.1051/parasite/2022059

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracts of wild Egyptian plants from the desert inhibit the growth of <i>Toxoplasma gondii</i> and <i>Neospora caninum in vitro</i>2022

    • Author(s)
      Abdou AM, Seddek AS, Abdelmageed N, Badry MO, Nishikawa Y
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 84 Issue: 7 Pages: 1034-1040

    • DOI

      10.1292/jvms.22-0159

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of dense granule antigen 7 in vertical transmission of Neospora caninum in C57BL/6 mice infected during early pregnancy2022

    • Author(s)
      Abdou AM, Ikeda R, Watanabe K, Furuoka H, Nishikawa Y
    • Journal Title

      Parasitol Int.

      Volume: 89 Pages: 102576-102576

    • DOI

      10.1016/j.parint.2022.102576

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Toxoplasma gondii GRA15 DNA Vaccine with a Liposomal Nanocarrier Composed of an SS-Cleavable and pH-Activated Lipid-like Material Induces Protective Immunity against Toxoplasmosis in Mice2021

    • Author(s)
      Hasan T, Kawanishi R, Akita H, Nishikawa Y
    • Journal Title

      Vaccines

      Volume: 10 Issue: 1 Pages: 21-21

    • DOI

      10.3390/vaccines10010021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Evaluation of Four Potent Neospora caninumDiagnostic Antigens Using Immunochromatographic Assay for Detection of Specific Antibody in Cattle2021

    • Author(s)
      Fereig RM, Abdelbaky HH, Nishikawa Y
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 10 Pages: 2133-2133

    • DOI

      10.3390/microorganisms9102133

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic characterization of Neospora caninum from aborted bovine fetuses in Hokkaido, Japan2021

    • Author(s)
      El-Alfy ES, Ohari Y, Shimoda N, Nishikawa Y
    • Journal Title

      Infect Genet Evol

      Volume: 92 Pages: 104838-104838

    • DOI

      10.1016/j.meegid.2021.104838

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Vaccination with Neospora GRA6 Interrupts the Vertical Transmission and Partially Protects Dams and Offspring against Neospora caninum Infection in Mice.2021

    • Author(s)
      Fereig RM, Abdelbaky HH, Nishikawa Y.
    • Journal Title

      Vaccines

      Volume: 9 Issue: 2 Pages: 155-155

    • DOI

      10.3390/vaccines9020155

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of some plant extracts from Egyptian herbal plants against <i>Toxoplasma gondii</i> tachyzoites <i>in vitro</i>2021

    • Author(s)
      Elazab ST, Soliman AF, Nishikawa Y.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 83 Issue: 1 Pages: 100-107

    • DOI

      10.1292/jvms.20-0458

    • NAID

      130007967856

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CXCR3-Dependent Immune Pathology in Mice following Infection with Toxoplasma gondii during Early Pregnancy.2021

    • Author(s)
      Nishida A, Ikeda R, Furuoka H, Nishikawa Y.
    • Journal Title

      Infect Immun.

      Volume: 89 Issue: 2

    • DOI

      10.1128/iai.00253-20

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Toxoplasma gondii Dense Granule Proteins 7, 14, and 15 Are Involved in Modification and Control of the Immune Response Mediated via NF-κB Pathway.2020

    • Author(s)
      Ihara F, Fereig RM, Himori Y, Kameyama K, Umeda K, Tanaka S, Ikeda R, Yamamoto M, Nishikawa Y.
    • Journal Title

      Front Immunol.

      Volume: 11 Pages: 1709-1709

    • DOI

      10.3389/fimmu.2020.01709

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NMR resonance assignments of the programmed cell death protein 5 (PDCD5) from Toxoplasma gondii.2020

    • Author(s)
      Lin MH, Yu TA, Chang CF, Nishikawa Y, Hsu CH.
    • Journal Title

      Biomol NMR Assign.

      Volume: 14 Issue: 2 Pages: 277-280

    • DOI

      10.1007/s12104-020-09961-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection.2020

    • Author(s)
      Maeta M, Miura N, Tanaka H, Nakamura T, Kawanishi R, Nishikawa Y, Asano K, Tanaka M, Tamagawa S, Nakai Y, Tange K, Yoshioka H, Harashima H, Akita H.
    • Journal Title

      Mol Pharm.

      Volume: 17 Issue: 4 Pages: 1237-1247

    • DOI

      10.1021/acs.molpharmaceut.9b01262

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serological detection of T. gondii infection in humans using an immunochromatographic assay based on dense granule protein 7.2020

    • Author(s)
      Ybanez RHD, Nishikawa Y.
    • Journal Title

      Parasitol Int.

      Volume: 76 Pages: 102089-102089

    • DOI

      10.1016/j.parint.2020.102089

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of antibodies against <i>Toxoplasma gondii</i> in cats using an immunochromatographic test based on GRA7 antigen2020

    • Author(s)
      Ybanez RHD, Kyan H, Nishikawa Y.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 82 Issue: 4 Pages: 441-445

    • DOI

      10.1292/jvms.19-0654

    • NAID

      130007829873

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Neospora caninum serodiagnostic antigens for bovine neosporosis.2020

    • Author(s)
      Abdelbaky HH, Nishimura M, Shimoda N, Hiasa J, Fereig RM, Tokimitsu H, Inokuma H, Nishikawa Y.
    • Journal Title

      Parasitol Int.

      Volume: 75 Pages: 102045-102045

    • DOI

      10.1016/j.parint.2019.102045

    • NAID

      120007004078

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Review on the Current Trends of Toxoplasmosis Serodiagnosis in Humans. (Review)2020

    • Author(s)
      Ybanez RHD, Ybanez AP, Nishikawa Y.
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: 10 Pages: 204-204

    • DOI

      10.3389/fcimb.2020.00204

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] From Signaling Pathways to Distinct Immune Responses: Key Factors for Establishing or Combating Neospora caninum Infection in Different Susceptible Hosts. (Review)2020

    • Author(s)
      Fereig RM, Nishikawa Y.
    • Journal Title

      Pathogens

      Volume: 9 Issue: 5 Pages: 384-384

    • DOI

      10.3390/pathogens9050384

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ネオスポラ感染による単球のミトコンドリア損傷と IL-1β産生は GRA7 とプロヒビチンの相 互作用が関与する2024

    • Author(s)
      Chen Yu、下田 直美、二瓶 浩一、錦織 充広、中村 柊、小柴 琢己、潮(渡邉) 奈々子、西川 義文
    • Organizer
      第93回日本寄生虫学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ole of Neospora caninum surface antigen 1 (NcSAG1) in the pathogenesis of neosporosis in non-pregnant and pregnant mice2023

    • Author(s)
      Md. Masudur Rahman、Hanan Abdelbaky、Naomi Shimoda、Tanjla Hasan、Nanako Ushio、Yoshifumi Nishikawa
    • Organizer
      第92回日本寄生虫学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ネオスポラ感染に対するケモカイン受容体 CXCR3 の感染防御機構への関与2023

    • Author(s)
      西川 義文、Hanan Abdelbaky、三橋 秀一郎、渡邊 謙一、潮 奈々子、 宮川 実紅、古岡 秀文
    • Organizer
      第92回日本寄生虫学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ネオスポラ感染に対する弱毒生ワクチンとしての NcGRA7 欠損株の防御効果2022

    • Author(s)
      Abdou Ahmed ,西川 義文
    • Organizer
      第91回日本寄生虫学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ウシのネオスポラ感染例における原虫および原虫由来タンパク質の脳内分布2022

    • Author(s)
      潮 奈々子 ,藤原 理央 ,渡邉 謙一 ,古林 与志安 ,西川 義文
    • Organizer
      第91回日本寄生虫学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ネオスポラ感染における原虫由来タンパク質の脳内分布2022

    • Author(s)
      潮 奈々子、藤原 理央、渡邉 謙一、古林 与志安、西 川 義文
    • Organizer
      165回日本獣医学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Extracts of Egyptian plants inhibit the growth of Toxoplasma gondii and Neospora caninum in vitro2022

    • Author(s)
      Abdou Ahmed、Seddek Abdel-latif、Abdelmageed Noha、Badry Mohamed、西川 義文
    • Organizer
      第165回日本獣医学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] ネオスポラの血清診断用イムノクロマトテストの開発2022

    • Author(s)
      Fereig Ragab、Abdelbaky Hanan、西川 義文
    • Organizer
      第165回日本獣医学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Role of dense granule antigen 7 on vertical transmission of Neospora caninum in mice2021

    • Author(s)
      Abdou Ahmed、池田 里奈、渡邉 謙一、古岡 秀文、西川 義文
    • Organizer
      第90回日本寄生虫学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Genetic characterization of Neospora caninum from aborted bovine fetuses in Hokkaido, Japan2021

    • Author(s)
      El-Sayed El-Alfy, Yuma Ohari, Naomi Shimoda, Yoshifumi Nishikawa
    • Organizer
      British Society for Parasitology, Parasites Online 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunization with Neospora GRA6 confers efficient protection against Neospora caninum infection in both non-pregnant and pregnant mice2021

    • Author(s)
      Ragab Fereig、下田 直美、Abdelbaky Hanan、西川 義文
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Possible effects of dense granule protein 7 on vertical transmission of Neospora caninum.2020

    • Author(s)
      Abdou Ahmed、池田里奈、古岡秀文、西川義文
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of Neospora caninum serodiagnostic antigens for bovine neosporosis.2020

    • Author(s)
      Abdelbaky Hanan、西村麻紀、下田直美、日浅淳、Fereig Ragab、時光宏三、猪熊壽、西川義文
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Serological detection of Toxoplasma infection in humans and cats using an immunochromatographic assay based on dense granule protein 7.2020

    • Author(s)
      Ybanez Rochelle、喜屋武向子、西川義文.
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Toxoplasma gondii dense granule protein 7, 14, 15が関与するNFκB経路を介した宿主免疫応答による感染病態の制御.2020

    • Author(s)
      猪原史成、梅田剛佑、Fereig Ragab、山本雅祐、西川義文.
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Neospora caninum由来のToxofilinタンパク質のワクチン効能に関する研究2020

    • Author(s)
      関口智史、徐剣、西川義文、Abdou Ahmed、朴龍洙
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Research-status Report
  • [Book] Methods Mol Biol2022

    • Author(s)
      Fereig RM, Nishikawa Y
    • Total Pages
      360
    • Publisher
      Humana New York, NY
    • ISBN
      9781071618882
    • Related Report
      2021 Research-status Report
  • [Book] 家畜伝染病ハンドブック(トキソプラズマ症を執筆)2020

    • Author(s)
      村上 賢二、彦野 弘一
    • Total Pages
      304
    • Publisher
      朝倉書店
    • ISBN
      9784254460384
    • Related Report
      2020 Research-status Report
  • [Remarks] 帯広畜産大学・原虫病研究センター・西川研究室

    • URL

      https://sites.google.com/site/nishihdlab/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report
  • [Remarks] &#11972;川研究室 X

    • URL

      https://twitter.com/Nishi_HD_LAB

    • Related Report
      2023 Annual Research Report
  • [Remarks] 帯広畜産大学・原虫病研究センター

    • URL

      http://www.obihiro.ac.jp/~protozoa/index.html

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report 2020 Research-status Report
  • [Remarks] 帯広畜産大学

    • URL

      https://www.obihiro.ac.jp

    • Related Report
      2022 Research-status Report 2020 Research-status Report
  • [Remarks] 帯広畜産大学・原虫病研究センター・生体防御学分野・西川研究室

    • URL

      https://sites.google.com/site/nishihdlab/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2025-01-30  

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