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Prophylactic and therapeutic HPV16 vaccine using yeast expressing chimeric L1 and E7 protein.

Research Project

Project/Area Number 15591735
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University

Principal Investigator

SASAGAWA Toshiyuki  Kanazawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30272975)

Co-Investigator(Kenkyū-buntansha) 浜 祐子  旭硝子(株), APSPEX・事業推進部研究開発グループ, 主幹
GIGA-HAMA Yuko  Asahi Glass Central Laboratory, Head of Research Group
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordshuman papillomavirus type 16 (HPV16) / cervical cancer / yeast / virus-like particles (VLP) / an edible vaccine / L1-E7 chimeric protein / prophylactic vaccine / therapeutic vaccine / ヒトパピローマウイルス / 粘膜免疫 / 腸管粘膜刺激ワクチン / HPV16型L1,E7蛋白 / 治療的ワクチン / 経口ワクチン / L1, E7蛋白
Research Abstract

High-risk HPV, such as HPV type 16 was the most important etiologic factor for cervical cancer, which is the secondary many cancer in women worldwide. Therefore, HPV vaccine development is one of the best ways to reduce the incidence of cervical cancer, especially in manu developing countries Koutsky et al. first demonstrate that HPV16-L1 virus-like particles (VLP), which was produced from yeast can protect HPV16-infection in women who undertook parenteral vaccination of the VLP. This suggests that VLP vaccine is highly effective against HPV16 infection. However, the parenteral VLP vaccine may be not useful in many developing countries, since it is very expensive and the injection procedure may be difficult to perform in such countries where medical stuffs are limited. We have found that an edible freeze-dried yeast vaccine containing HPV16-L1 protein enhanced with intranasal administration of a suboptimal dose of HPV16-VLP is able to induce HPV16-specific antibody responses in mice mo … More del system. In the present study, we tried to make recombinant yeast expressing L1-E7 chimeric protein in order to synthesize VLP containing oncoprotein E7. We made three different-sized L1-E7 DNA constracts which contained full-length of E7 and truncated L1 genes, and transfected them into yeast, and had got three strains of yeast expressing 57kD, 63KD, and 67KD proteins, respectively. Since we succeeded to purify VLP from the yeast producing 63KD protein, we used this strain for an edible yeast vaccine in the mice model system. If the chimeric L1-E7 VLP induced antibody against HP16, and incorporated E7 protein induced cytotoxic T lymphocytes killing HPV16-infected cell, this vaccine might be useful as prophylactic and therapeutic vaccine against HPV16 infection. In the preliminary experiment, we found that this vaccine induces HPV16 L1 antibody in the immunized mice. Now we are going to investigate this further, and to test the cytotoxic T lymphocyte response to HPV16-E7 protein in the mice Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (34 results)

All 2005 2004 2003 Other

All Journal Article (24 results) Book (3 results) Patent(Industrial Property Rights) (2 results) Publications (5 results)

  • [Journal Article] A human papillomavirus type16 vaccine by oral delivery of L1 protein2005

    • Author(s)
      Sasagawa T., Tani M.et al.
    • Journal Title

      Virus Res. 101

      Pages: 81-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sexual behavior and cervical high-risk human papillomavirus (HPV) infections in Japanese women2005

    • Author(s)
      Sasagawa T, Yasuda H, et al.
    • Journal Title

      Sexually Transmitted Infection 81

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sexual behavior and cervical high-risk human papillomavirus (HPV) infections in Japanese women2005

    • Author(s)
      Sasagawa T, H.Yasuda, M.Tani, W.Basha et al.
    • Journal Title

      Sex.Trans.Infect.(STI) 81

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A human papillomavirus type 16 vaccine by oral delivery of L1 protein.2005

    • Author(s)
      Sasagawa T, M.Tani, W.Basha, RC.Rose, H.Tohda, Y.Giga-Hama, KK.Azar, H.Yasuda, A.Sakai, M.Inoue.
    • Journal Title

      Virus Res. 101

      Pages: 81-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A human papillomavirus type16 vaccine by oral delivery of L1 protein2005

    • Author(s)
      Sasagawa T., Tani M.et al.
    • Journal Title

      Virus Research (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sexual behavior and cervical high-risk human papillomavirus(HPV) infections in Japanese women2005

    • Author(s)
      Sasagawa T, Yasuda H., et al.
    • Journal Title

      Sexually Transmitted Infection (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased secretion patterns of Interleukin-10 and tumor necrosis factor-alpha in cervical squamous intraepithelial lesions2004

    • Author(s)
      Azar KK, H.Yasuda, M.et al.
    • Journal Title

      Human Pathology 35

      Pages: 1376-1384

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased secretion patterns of Interleukin-10 and tumor necrosis factor-alpha in Cervical squamous intraepithelial lesions2004

    • Author(s)
      Azar KK, H.Yasuda, M.Tani, W.Basha et al.
    • Journal Title

      Human Pathol. 35

      Pages: 1376-1384

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased secretion patterns of Interleukin-10 and tumor nerosis factor-alpha in cervical squamous intraepithelial lesions2004

    • Author(s)
      Azar KK, H.Yasuda, M.et al.
    • Journal Title

      Human Pathology 35

      Pages: 1376-1382

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human papillomavirus infection and cervical cancer2003

    • Author(s)
      Sasagawa T.
    • Journal Title

      Biomedical Reviews 14

      Pages: 75-93

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES.2003

    • Author(s)
      Kim SJ, Lee C, Lee SY et al.
    • Journal Title

      Gene Therapy 10

      Pages: 1268-1273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expression of Epstein-Barr virus in thyroid carcinoma correlated with tumor progression. 34, 1170-1177, 2003.2003

    • Author(s)
      Shimakage M, Kawahara K. et al.
    • Journal Title

      Human pathology 34

      Pages: 1170-1177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pro-apoptotic ASY/Nogo-B protein associates with ASYIP2003

    • Author(s)
      Qi B, Qi Y, Watari A, et al.
    • Journal Title

      J Cell Physiol. 196

      Pages: 312-318

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids2003

    • Author(s)
      Sasagawa T, Rose RC et al.
    • Journal Title

      Int J Cancer. 104

      Pages: 329-335

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation. 412, 13-19, 2003.2003

    • Author(s)
      Minemoto Y, Uchida S. et al.
    • Journal Title

      Arch.Biochem.and Biophysics 412

      Pages: 13-19

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.2003

    • Author(s)
      Minemoto Y, Uchida S. et al.
    • Journal Title

      Arch.Biochem.and Biophysics 412

      Pages: 13-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids.2003

    • Author(s)
      Sasagawa T, Rose RC et al.
    • Journal Title

      Int J Cancer. 104

      Pages: 329-335

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.2003

    • Author(s)
      Qi B, Qi Y, Watari A, Yoshioka N, Sasagawa T et al.
    • Journal Title

      J.Cell.Physiol. 196(2)

      Pages: 312-318

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of Epstein-Barr virus in thyroid carcinoma correlated with tumor progression.2003

    • Author(s)
      Shimakage M, Kawahara K. et al.
    • Journal Title

      Human pathology 34

      Pages: 1170-1177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES.2003

    • Author(s)
      Kim SJ, Lee C, Lee SY, Kim I, Sasagawa T et al.
    • Journal Title

      Gene Ther. 10(15)

      Pages: 1268-1273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human papillomavirus infection and cervical cancer.2003

    • Author(s)
      Sasagawa T.
    • Journal Title

      Biomedical Reviews 14

      Pages: 75-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids.2003

    • Author(s)
      Sasagawa T, Rose RC et al.
    • Journal Title

      International Journal of Cancer 104

      Pages: 329-335

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.2003

    • Author(s)
      Qi B, Qi Y, Watari A, et al.
    • Journal Title

      Journal of Cell Physiology 196

      Pages: 312-318

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 【子宮頚癌・子宮体癌・卵巣癌の診断と治療 最新の研究動向】子宮頚癌 子宮頚癌の診断 遺伝子診断

    • Author(s)
      笹川寿之
    • Journal Title

      日本臨床 2004

      Volume: 62 Issue: 増刊10 Pages: 103-108

    • Related Report
      2004 Annual Research Report
  • [Book] 産婦人科の実際 52巻2003

    • Author(s)
      笹川寿之
    • Total Pages
      8
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 金沢大学保健管理センターセンターだより No.222003

    • Author(s)
      笹川寿之
    • Total Pages
      5
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 日本臨床 62巻 増刊102003

    • Author(s)
      笹川寿之
    • Total Pages
      5
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許出願2004

    • Inventor(s)
      笹川 寿之, 東田 英毅 他
    • Industrial Property Rights Holder
      旭硝子, 金沢大学
    • Industrial Property Number
      2004-263580
    • Filing Date
      2004-09-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 特許2004

    • Inventor(s)
      笹川寿之, 浜祐子, 東田
    • Industrial Property Rights Holder
      金沢大学, 旭硝子
    • Filing Date
      2004-09-10
    • Related Report
      2004 Annual Research Report
  • [Publications] Minemoto Y, Sasagawa T et al.: "Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation"Arch Biochem Biophys.. 412. 13-19 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasagawa T, Rose RC, et al.: "Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids"Int J Cancer. 104. 328-335 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Qi B, Qi Y et al.: "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP"J Cell Physiol.. 196(2003 Aug ; 196(2)). 312-318 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim SJ, Lee C, Lee SY et al.: "Enhanced immunogenicity of human papillomavirus 16 L1 genetic vaccines fused to an ER-targeting secretory signal peptide and RANTES."Gene Therapy. 10. 1268-1273 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimakage M, Kawahara K, Sasagawa T et al.: "Expression of Epstein-Barr virus in thyroid carcinoma correlates with tumor progression"Hum Pathol.. 34(2003 Nov ; 34(11)). 1170-1177 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2017-11-09  

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