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Vaccine development of mosquito-borne infectious diseases using molecular controllable multiple antigen-displaying virus-like particles

Research Project

Project/Area Number 20H00411
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionShizuoka University

Principal Investigator

PARK Enoch Y.  静岡大学, グリーン科学技術研究所, 教授 (90238246)

Co-Investigator(Kenkyū-buntansha) 鈴木 亮介  国立感染症研究所, ウイルス第二部, 室長 (50342902)
筏井 宏実  北里大学, 獣医学部, 准教授 (80327460)
加藤 竜也  静岡大学, 農学部, 教授 (00397366)
宮崎 剛亜  静岡大学, グリーン科学技術研究所, 准教授 (30775721)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2023: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2022: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2021: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2020: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Keywordsウイルス様粒子 / カイコ / デングウイルス / マラリア / エンベロープ / SpyTag Sptcatcher / ワクチン / 抗原提示 / マラリア抗原 / タンパク質精製 / 蚊媒介感染症 / 抗原提示ウイルス様粒子 / 抗原提示型ウイルス様粒子 / 磁性ナノ粒子 / 磁気ナノ粒子 / 多抗原提示型ウイルス様粒子
Outline of Research at the Start

ウイルス様粒子(Virus-like particle、以下VLP)は、近年有望なワクチン素材として期待されている。本研究では、抗原とVLPの表面を化学結合する分子制御が可能な新規抗原提示法を開発し、複数の抗原を均一にVLPの表面に提示できる多抗原提示型VLP(以下多価VLP)の創成と磁気ナノ粒子を活用した多価VLPの革新的精製法を開発する。それを蚊媒介感染症、中でも、デング熱に対するマウスでの中和抗体産生誘導能評価やマラリアを対象にした感染防御試験によりその効果を実証する。これにより難治性原虫感染症に対する多価VLPワクチンを作製するカイコバイオファクトリーを世界に先駆けて確立する。

Outline of Final Research Achievements

In this study, norovirus-like, canine parvovirus-like, and dengue capsid-like particles, potential vaccine candidates, were expressed in silkworm larvae. Multivalent VLPs were successfully prepared by displaying two antigens of malaria, or four dengue virus serotypes antigens on the surface of the VLPs using a chemical binding method. These multivalent VLPs were found to have high antibody generation in animal experiments. Significantly, the dengue tetravalent VLPs showed sufficient neutralizing activity against the four dengue serotypes. These results demonstrated the efficacy of the multivalent VLPs prepared by silkworms as a vaccine candidate and initiatively established the basis for a silkworm-based multivalent VLP vaccine.

Academic Significance and Societal Importance of the Research Achievements

本研究では、最近ワクチン候補として注目されているウイルス様粒子(VLP)をカイコで発現・精製した。さらにこれらのVLPの表面に複数の抗原を化学結合した複数の抗原提示に成功した。作製した多価VLPは動物実験で、高い抗体産生が認められ、またデングウイルスの中和活性も立証された。
本研究成果は、古くから家畜化され、非常に安全なタンパク質発現系として認められているカイコがシルク以外にバイオ産業への貢献が期待できるものである。また、1つのVLPで複数のウイルスによる感染症を防御することができるため、将来安心・安全な社会つくりに大いに貢献できるものである。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Comments on the Screening Results   Annual Research Report
  • Research Products

    (52 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (5 results) Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 6 results) Presentation (31 results) (of which Int'l Joint Research: 16 results,  Invited: 8 results) Remarks (2 results)

  • [Int'l Joint Research] Sabar Pambudi/Center of Pharmaceut. & Med. Technol./National Research and Innovation Agency(インドネシア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Sabar Pambudi/Center of Pharmaceut. & Med. Technol./National Research and Innovation Agency(インドネシア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Sabar Pambudi/Center of Pharmaceut. & Med. Technol./National Research and Innovation Agency(インドネシア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Technical University of Braunschweig(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] BPPT/University Indonesia(インドネシア)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Expression and Purification of Porcine Rotavirus Structural Proteins in Silkworm Larvae as a Vaccine Candidate2023

    • Author(s)
      Kato Tatsuya、Kakuta Tatsuki、Yonezuka Ami、Sekiguchi Tomofumi、Machida Yuki、Xu Jian、Suzuki Tohru、Park Enoch Y.
    • Journal Title

      Molecular Biotechnology

      Volume: 65 Issue: 3 Pages: 401-409

    • DOI

      10.1007/s12033-022-00548-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Display of multiple proteins on engineered canine parvovirus-like particles expressed in cultured silkworm cells and silkworm larvae2023

    • Author(s)
      Xu Jian、Sekiguchi Tomofumi、Boonyakida Jirayu、Kato Tatsuya、Park Enoch Y.
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 11 Pages: 1096363-1096363

    • DOI

      10.3389/fbioe.2023.1096363

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of Modular Protein Display Efficiency in SpyTag-Implemented Norovirus-like Particles2022

    • Author(s)
      Boonyakida Jirayu、Khoris Indra Memdi、Nasrin Fahmida、Park Enoch Y.
    • Journal Title

      Biomacromolecules

      Volume: 24 Issue: 1 Pages: 308-318

    • DOI

      10.1021/acs.biomac.2c01150

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immunostimulation of shrimp through oral administration of silkworm pupae expressing VP15 against WSSV2022

    • Author(s)
      Boonyakida Jirayu、Nakanishi Takafumi、Satoh Jun、Shimahara Yoshiko、Mekata Tohru、Park Enoch Y.
    • Journal Title

      Fish & Shellfish Immunology

      Volume: 128 Pages: 157-167

    • DOI

      10.1016/j.fsi.2022.07.043

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo enzymatic digestion of HRV 3C protease cleavage sites-containing proteins produced in a silkworm-baculovirus expression system2022

    • Author(s)
      Xu Jian、Nakanishi Takafumi、Kato Tatsuya、Park Enoch Y.
    • Journal Title

      Bioscience Reports

      Volume: 42 Issue: 6

    • DOI

      10.1042/bsr20220739

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual display hemagglutinin 1 and 5 on the surface of enveloped virus-like particles in silkworm expression system2022

    • Author(s)
      Goffar Muzajjad Gozal、Deo Vipin Kumar、Kato Tatsuya、Park Enoch Y.
    • Journal Title

      Protein Expression and Purification

      Volume: 197 Pages: 106106-106106

    • DOI

      10.1016/j.pep.2022.106106

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Humoral immune response induced with dengue virus-like particles serotypes 1 and 4 produced in silkworm2022

    • Author(s)
      Utomo Doddy Irawan Setyo、Pambudi Sabar、Park Enoch Y.
    • Journal Title

      AMB Express

      Volume: 12 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s13568-022-01353-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two-step purification of tag-free norovirus-like particles from silkworm larvae (Bombyx mori)2022

    • Author(s)
      Boonyakida Jirayu、Utomo Doddy Irawan Setyo、Soma Fahmida Nasrin、Park Enoch Y.
    • Journal Title

      Protein Expression and Purification

      Volume: 190 Pages: 106010-106010

    • DOI

      10.1016/j.pep.2021.106010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of antigenic domains and peptides from VP15 of white spot syndrome virus and their antiviral effects in Marsupenaeus japonicus2021

    • Author(s)
      Boonyakida Jirayu、Xu Jian、Satoh Jun、Nakanishi Takafumi、Mekata Tohru、Kato Tatsuya、Park Enoch Y.
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 12766-12766

    • DOI

      10.1038/s41598-021-92002-8

    • NAID

      120007126510

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ni-modified magnetic nanoparticles for affinity purification of His-tagged proteins from the complex matrix of the silkworm fat body2020

    • Author(s)
      Minkner Robert、Xu Jian、Takemura Kenshin、Boonyakida Jirayu、Watzig Hermann、Park Enoch Y.
    • Journal Title

      Journal of Nanobiotechnology

      Volume: 18 Issue: 1 Pages: 159-159

    • DOI

      10.1186/s12951-020-00715-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Production of dengue virus-like particles serotype-3 in silkworm larvae and their ability to elicit a humoral immune response in mice2020

    • Author(s)
      Utomo Doddy Irawan Setyo、Pambudi Sabar、Sjatha Fithriyah、Kato Tatsuya、Park Enoch Y.
    • Journal Title

      AMB Express

      Volume: 10 Issue: 1 Pages: 147-147

    • DOI

      10.1186/s13568-020-01087-3

    • NAID

      120006877899

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preparation of divalent antigen-displaying enveloped virus-like particles using a single recombinant Bombyx mori nucleopolyhedrovirus bacmid in silkworms2020

    • Author(s)
      Kato Tatsuya、Machida Yuki、Takemura Kenshin、Xu Jian、Park Enoch Y.
    • Journal Title

      Journal of Biotechnology

      Volume: 323 Pages: 92-97

    • DOI

      10.1016/j.jbiotec.2020.08.002

    • NAID

      120006877897

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A systematic and methodical approach for the efficient purification of recombinant protein from silkworm larval hemolymph2020

    • Author(s)
      Minkner Robert、Xu Jian、Zagst Holger、Watzig Hermann、Kato Tatsuya、Oltmann-Norden Imke、Park Enoch Y.
    • Journal Title

      Journal of Chromatography B

      Volume: 1138 Pages: 121964-121964

    • DOI

      10.1016/j.jchromb.2019.121964

    • NAID

      120006777506

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of secretion domain of Neospora caninum profilin2020

    • Author(s)
      Suhaimi Hamizah、Xu Jian、Kato Tatsuya、Setyo Utumo Doddy Irawan、Sekiguchi Tomofumi、Park Enoch Y.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 522 Issue: 1 Pages: 8-13

    • DOI

      10.1016/j.bbrc.2019.11.056

    • NAID

      120006776430

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] Norovirus-based platform for modular displaying of antigenic protein candidates for mosquito-borne infectious diseases2024

    • Author(s)
      Jirayu Boonyakida, Enoch Y. Park
    • Organizer
      日本農芸化学会2024年大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Envelope Domain III (EDIII) displaying Dengue virus-like particle: A tetravalent Virus Like Particle (VLP) using silkworm expression system2024

    • Author(s)
      Krishna Raja Muthuraman, Jirayu boonyakida, and Enoch Y. Park
    • Organizer
      日本農芸化学会2024年大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Modular displaying of dengue envelope protein domain III (EDIII) on SpyTagged-Norovirus-like particles2023

    • Author(s)
      Jirayu Boonyakida, Enoch Y. Park
    • Organizer
      2023年度日本生物工学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] カイコバイオファクトリーによる持続可能な循環型ものづくり2023

    • Author(s)
      朴 龍洙
    • Organizer
      第13回シーズ&ニーズビジネスマッチング研究発表会
    • Related Report
      2023 Annual Research Report
  • [Presentation] SILKWORM BIOFACTORY AS A VIRUS-LIKE PARTICLES PREPARATION PLATFORM2023

    • Author(s)
      Enoch Y. Park
    • Organizer
      2023 30th FAOBMB and 8th BMB Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SpyTagged-norovirus-like Particle as a Modular Platform for Bivalent Displaying of CSP and MSP119 Proteins from Plasmodium yoelii2023

    • Author(s)
      Jirayu Boonyakida, Kazuhiko Nakayama, Kodai Kusakisako, Hiromi Ikadai, and Enoch Y. Park
    • Organizer
      2023 30th FAOBMB and 8th BMB Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PHYSIOCHEMICAL ANALYSIS OF SILKWORM LARVAE EXPRESSED CANINE PARVO VIRUS LIKE PARTICLE DISPLAYING ENVELOPE DOMAIN (EDIII) OF DENGUE VIRUS SEROTYPES2023

    • Author(s)
      Krishna Raja Muthuraman, Jirayu boonyakida, and Enoch Y. Park
    • Organizer
      2023 30th FAOBMB and 8th BMB Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カイコバイオファクトリーによるワクチン基盤技術の構築2023

    • Author(s)
      朴 龍洙
    • Organizer
      科研費研究成果トピックス
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] SILKWORM BIOFACTORY AS A VIRUS-LIKE PARTICLES PREPARATION PLATFORM2023

    • Author(s)
      Enoch Y. Park
    • Organizer
      International Seminar and Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 複数のタンパク質を提示した ウイルス様粒子の作製2023

    • Author(s)
      朴 龍洙
    • Organizer
      2023年度中部乳酸菌研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Silkworm Biofactory as a Potential Protein Expression System and its Possibility2023

    • Author(s)
      Enoch Y. Park
    • Organizer
      International Conference for Green Science and Technology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Immunological Evaluation of Monovalent Capsid Virus-Like Particle Displayed Envelope Domain III (EDIII) of Dengue Serotype 2 using Silkworm Larvae2023

    • Author(s)
      Krishna Raja Muthuraman, Doddy Irawan Setyo Utomo, Jirayu boonyakida, Mami Matsuda, Ryouske Suzuki, and Enoch Y Park
    • Organizer
      International Conference for Green Science and Technology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Virus-like particles from Silkworm2023

    • Author(s)
      Enoch Y. Park
    • Organizer
      A short meeting Nanobiotechnology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] From Silkroad to Bioroad2023

    • Author(s)
      Enoch Y. Park
    • Organizer
      BK21 4th Interdisciplinary Program in IT-Bio Convergence System "Change the future agriculture with new farming technology"
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Norovirus-like particles as a modular platform for displaying antigenic proteins from Plasmodium yoelii2023

    • Author(s)
      Jirayu Boonyakida, Enoch Y. Park
    • Organizer
      日本農芸化学会2023年大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] イヌパルボウイス様粒子の表面への複数のタンパク質の提示2023

    • Author(s)
      朴 龍洙、関口智史、Jirayu Boonyakida、徐 剣、加藤竜也
    • Organizer
      日本農芸化学会2023年大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ウイルス感染症の検出とカイコによるワクチン開発2022

    • Author(s)
      朴 龍洙
    • Organizer
      浜松工業会静岡支部2022年度 支部総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] カイコを用いたウイルス様粒子の作製と抗原提示2022

    • Author(s)
      朴 龍洙
    • Organizer
      化学工学会53回秋季大会バイオ部会シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] カイコを用いたブタロタウイルス構造タンパク質の発現2022

    • Author(s)
      加藤竜也、角田達紀、米塚亜美、町田佑樹、関口智史、徐剣、鈴木亨、朴龍洙
    • Organizer
      2022年度日本生物工学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] イヌパルボウイルス様粒子の作製とEGFPの提示2022

    • Author(s)
      朴龍洙、関口智史、ブーニャキダジラユ、徐剣、加藤竜也
    • Organizer
      2022年度日本生物工学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Immunostimulation of shrimp through oral administration of silkworm pupae expressing VP15 against WSSV2022

    • Author(s)
      Jirayu Boonyakida, Takafumi Nakanishi, Jun Satoh, Yoshiko Shimahara, Tohru Mekata, and Enoch Y. Park
    • Organizer
      2022年度日本生物工学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Display technology in virus-like particles using silkworm expression system2022

    • Author(s)
      朴 龍洙
    • Organizer
      NIPER-PHARMACO2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Expression of dengue virus 1-4serotypes envelope domain EDIII using silkworm expression system and their display on dengue virus-like particle2022

    • Author(s)
      Krishna Raja Muthuraman, Enoch Y. Park
    • Organizer
      NIPER-PHARMACO2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Silkworm pupa as a vehicle for delivering VP15-derived products through oral administration for immunization of kuruma shrimp2022

    • Author(s)
      Jirayu Boonyakida, Takafumi Nakanishi, Jun Satoh, Yoshiko Shimahara, Tohru Mekata, and Enoch Y. Park
    • Organizer
      The 4th Congress of the International Society of Fish and Shellfish Immunology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Purification and characterization of norovirus-like particle and its SpyTag-variants from silkworm (Bombyx mori)2021

    • Author(s)
      Jirayu Boonyakida, Doddy Irawan Setyo Utomo, Jian Xu, Enoch Y. Park
    • Organizer
      第73回(2021年)日本生物工学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The eliciting capability a humoral immune response in a mouse model induced with dengue virus-like particles serotypes 1 and 4 produced in silkworm larvae2021

    • Author(s)
      Doddy Irawan Setyo Utomo1, Sabar Pambudi, Enoch Y. Park
    • Organizer
      第73回(2021年)日本生物工学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Decoration of GII.4 Norovirus-like Particles via SpyTag/SpyCatcher Bioconjugation System for a Modular Protein-displaying Platform2021

    • Author(s)
      Jirayu Boonyakida, Fahmida Nasrin, Indra Memdi Khoris, and Enoch Y. Park
    • Organizer
      The 1th SU-CNU Joint Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of an efficient antigen display system for Virus-Like Particles in silkworm2020

    • Author(s)
      Tomofumi Sekiguchi、Enoch Y. Park
    • Organizer
      International e-workshop on Biosensors 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dengue Virus-like Particles Assembly from Structural Proteins Expressed in Silkworm and Characterization2020

    • Author(s)
      Doddy Irawan Setyo Utomo、Enoch Y. Park
    • Organizer
      7th International symposium toward the future of advanced researches in Shizuoka University (ISPAR-SU2021)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression and purification of White spot syndrome virus antigen protein using silkworm expression system2020

    • Author(s)
      Takafumi Nakanishi、Enoch Y. Park
    • Organizer
      International e-workshop on Biosensors 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of effective peptide derived from WSSV-VP15 for protection of Masupenaeus japonicus against WSSV2020

    • Author(s)
      Jirayu Boonyakida、Jian Xu、Jun Satoh、Takafumi Nakanishi、Toru Mekata、Tatsuya Kato, and Enoch Y. Park
    • Organizer
      7th International symposium toward the future of advanced researches in Shizuoka University (ISPAR-SU2021)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 静岡大学教員データベース

    • URL

      https://tdb.shizuoka.ac.jp/RDB/public/Default2.aspx?id=10747&l=0

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks] 静岡大学生物工学研究室

    • URL

      http://www.agr.shizuoka.ac.jp/c/biotech/

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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