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Development of hantavirus vaccine and rapid diagnosis kit by using soluble recombinant envelope glycoproteins

Research Project

Project/Area Number 13556046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Applied veterinary science
Research InstitutionHokkaido University

Principal Investigator

MORIMATSU Kumiko  Hokkaido Univ., Grad. School of Med., Inst., 大学院・医学研究科, 助手 (90220722)

Co-Investigator(Kenkyū-buntansha) ONO Eriko  Merial Japan Limited, Res., つくば明野ラボラトリーズ, 研究員
MORIMATSU Masami  Iwate Univ., fac. of Agr., Asso. Prof., 農学部, 助教授 (70241370)
KARIWA Hiroaki  Hokkaido Univ., Grad. School of Vet. med., Asso. Prof., 大学院・獣医学研究科, 助教授 (70224714)
ARIKAWA Jiro  Hokkaido Univ., Grad. School of Med., Prof., 大学院・医学研究科, 教授 (10142704)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordshantavirus / envelope protein / antigenicity / vaccine / diagnosis / purification
Research Abstract

1. It was clarified that recombinant Hantavirus envelope glycoproteins G1 and G2 (GPs) had the cell-fusion activity by using CAG promotor-expression system. Fusion-responsible epitope on GPs was found to locate in the neutralization (FRNT)-relating epitope. Therefore, the recombinant GPs was considered to possess neutralization-and fusion-relating epitopes. In addition, hantavirus nucleocapsid (N) protein was also expressed in mammalian cells by using same vector. As the result the N protein may suppress that expression and transportation of the envelope protein. It was also shown that the virus like particle was not formed by GPs and N protein alone.
2. By using recombinant GPs, pseudotype vesicular stomatitis virus (VSV) enveloped with hantavirus GPs altered to VSV G protein was produced (VSVΔG*HTN). Similar pseudotype VSV was produced with recombinant GPs of Seoul virus (VSVΔG*SEO). These pseudotypes were applied to rapid neutralization assay as safety alternatives of authentic viruses. These pseudotype virus particles were also applied to vaccination as alternatives to authentic virion. Mice were immunized with soluble recombinant GPs or pseudotype virion. In mice immunized with soluble recombinant GPs, FRNT antibody was not detected. Contrary, in mice immunized with VSVΔG*HTN virion, FRNT antibody was detected. Challenge administration of hantavirus was carried out by s.c. inoculation of 4 FFU of hantavirus. These mice did not show the elevation of anti-N antibody and hantavirus specific CD8 T cell response, indicating that the FRNT antibody could protect mice from hantavirus infection. On the other hand, all control mice immunized with VSVΔG*G or PBS could not escape from hantavirus infection. These results indicated that packaged recombinant GPs on VSV particle were possible to induce protective FRNT antibody. This study shows that novel approach for the development of vaccination of viruses that have difficulties in preparation of authentic virus particles.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Jin, H.K.et al.: "Mouse Mx2 protein inhibits Hantavirus but not Influenza virus replication."Arch Virol. 146. 41-49 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K. et al.: "Truncated Hantavirus Nucleocapsid Proteins for Serotyping Hantaan, seoul, and Dobrava Hantavirus Infections."J Clin Microbiol. 39(7). 2397-2404 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa, J. et al.: "Epidemiology and epizootiology of hantavirus infection in Japan."JPN J Infect Dis. 54(3). 95-102 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariwa, H. et al.: "Epizootiological survey of hantavirus among rodent species in Ningxia Hui Autonomous Province, China."JPN J Vet Res. 49(2). 105-114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto, H. et al.: "Microbiological Contamination in Genetically Modified animals and proposals for a microbiological Test Standard for National Universities in Japan."Exp Anim. 50(5). 397-407 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murphy, M.E. et al.: "Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus."J Vet Med Sci. 63(6). 637-645 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M. et al.: "No Significant Differences Were Observed in the Amounts of DNA Strand breaks Produced by Copper between Male and Female Liver Cells of Long-Evans Cinnamon (LEC) Strain Rats."J Vet Med Sci. 63(10). 1109-1113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lokugamage, K. et al.: "Genetic Characterization of Hantaviruses Transmitted by the Korean Field Mouse (Apodemus peninsulae), Far East Russia."Emerg Infect Dis. 8(8). 768-776 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M. et al.: "Hepatic Iron Accumulation Is Not Directly Associated With Induction of DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon (LEC) Rats."Exp Anim. 51(1). 43-48 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M. et al.: "High sensitivity of thymocytes of LEC strain rats to induction of apoptosis by X-irradiation"J Vet Med Sci. 64(7). 597-601 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Endoh, D. et al.: "Protective Effect of a Lignan-Containing Flaxseed Extract against CCl4-Induced Hepatic Injury."J Vet Med. 64(9). 761-765 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshimatsu, K. et al.: "The multimerization of hantavirus nucleocapsid protein depends on type-specific epitopes."J Virol. 77(2). 943-952 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogino, M. et al.: "Use of VSV pseudotypes bearing Hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test."Clin Diag Lab Immun. 10(1). 154-160 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda, A. et al.: "Association of the nucleocapsid protein (NP) of Hantaan virus (HTNV) with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9 (Ubc9)."Virology. 305. 288-297 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takakura, A et al.: "Establishment of an Enzyme-Linked Immunosorbent Assay for Detection of Hantavirus Antibody of Rats Using a Recombinant of Nucleocapsid Protein Expressed in Escherichia coli."Exp Anim. 52(1). 25-30 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshii, K. et al.: "Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis."J Virol Methods. 108(2). 171-179 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K. et al.: "Hantavirus-Specific CD8+-T-Cell Responses in Newborn Mice Persistently Infected with Hantaan Virus."J Virol. 77(15). 8408-8417 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyamoto, H. et al.: "Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype."Arch Virol. 148. 1543-1556 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, B.H.et al.: "Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species."Arch Virol. 148(10). 1885-1897 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, B.H.et al.: "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules."Virus Res. 98(1). 83-91 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariwa, H. et al.: "Synthesis of Seoul virus RNA and structural proteins in cultured cells."Arch Virol. 148(9). 1671-1685 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sin, H.K.et al.: "Mouse Mx2 protein inhibits Hantavirus but not Influenza virus replication."Arch Virol. 146. 41-49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K. et al.: "Truncated Hantavirus Nucleocapsid Proteins for Serotyping Hantaan, Seoul, and Dobrava Hantavirus Infections."J Clin Microbiol. 39(7). 2397-2404 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa, J. et al.: "Epidemiology and epizootiology of hantavirus infection in Japan."JPN J Infect Dis. 54(3). 95-102 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariwa, H. et al.: "Epizootiological survey of hantavirus among rodent species in Ningxia Hui Autonomous Province, China."JPN J Vet Res. 49(2). 105-114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto, H. et al.: "Microbiological Contamination in Genetically Modified animals and proposals for a mierobiological Test Standard for National Universities in Japan."Exp Anim. 50(5). 397-407 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murphy, M.E. et al.: "Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus."J Vet Med Sci. 63(6). 637-645 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M. et al.: "No Significant Differences Were Observed in the Amounts of DNA Strand breaks Produced by Copper between Male and Female Liver Cells of Long-Evans Cinnamon (LEC) Strain Rats."J Vet Med Sci. 63(10). 1109-1113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lokugamage, K. et al.: "Genetic Characterization of Hantaviruses Transmitted by the Korean Field Mouse (Apodemus peninsulae), Far East Russia."Emerg Infect Dis. 8(8). 768-776 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M. et al.: "Hepatic Iron Accumulation Is Not Directly Associated With Induction of DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon (LEC) Rats."Exp Anim. 51(1). 43-48 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi, M.et al.: "High sensitivity of thymocytes of LEC strain rats to induction of apoptosis by X-irradiation."J Vet Med Sci. 64(7). 43-48 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Endoh, D. et al.: "Protective Effect of a Lignan-Containing Flaxseed Extract against CC14-Induced Hepatic Injury."J Vet Med Sci. 64(9). 761-765 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshimatsu, K. et al.: "The Multimerization of hantaviius nucleocapsid protein depends on type-specific epitopes."J Virol. 77(2). 943-952 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogino, M. et al.: "Use of VSV pseudotypes bearing Hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test."Clin Diag Lab Immun. 10(1). 154-160 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda., A.et al.: "Association of the nucleocapsid protein (NP) of Hantaan virus (HTNV) with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9(Ubc9)."Virology. 305. 288-297 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takakura, A. et al.: "Establishment of an Enzyme-Linked Immunosorbent Assay for Detection of Hantavirus Antibody of Rats Using a Recombinant of Nucleocapsid Protein Expressed in Escherichia coli."Exp Anim. 52(1). 25-30 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshii, K. et al.: "Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis."J Virol Methods. 108(2). 171-179 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Araki, K. et al.: "Hantavirus-Specific CD8+-T-Cell Responses in Newborn Mice Persistently Infected with Hantaan Virus."J Virol. 77(15). 8408-8417 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyamoto, H. et al.: "Serological analysis of hemorrhagic fever with renal syndrome(HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype."Arch Virol. 148. 1543-1556 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, B.H.et al.: "Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species."Arch Viral. 148(10). 1885-1897 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee, B.H.et al.: "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules."Virus Res. 98(1). 83-91 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariwa, H.et al.: "Synthesis of Seoul virus RNA and structural proteins in cultured cells."Arch Virol. 148(9). 1671-1685 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshii, K. et al.: "Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis"J Virol Methods. 108(2). 171-179 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Araki, K. et al.: "Hantavirus-Specific CD8+-T-Cell Responses in Newborn Mice Persistently Infected with Hantaan Virus"J Virol. 77(15). 8408-8417 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyamoto, H. et al.: "Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype"Arch Virol. 148. 1543-1556 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lee, B.H.et al.: "Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species"Arch Virol. 148(10). 1885-1897 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lee, B.H.et al.: "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules"Virus Res. 98(1). 83-91 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kariwa, H. et al.: "Synthesis of Seoul virus RNA and structural proteins in cultured cells"Arch Virol. 148(9). 1671-1685 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lokugamage, K. et al.: "Genetic Characterization of Hantaviruses Transmitted by the Korean Field Mouse (Apodemus peninsula), Far East Russia"Emerging Infectious Diseases.. 8(8). 768-776 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimatsu, K. et al.: "Themultimerization of hantavirus nucleocapsid protein depends on type-specific epitopes"Journal of Virology. 77(2). 943-952 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogino, M. et al.: "Use of VSV pseudotypes bearing Hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test"Clin. Diag. Lab. lmmun.. 10(1). 154-160 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maeda, A. et al.: "Association of the nucleocapsid protein (NP) of Hantaan virus (HTNV) with small, ubiquitin-like modifier-i (SUMO-1 conjugating enzyme 9(Ubc 9)"Virology. 305. 288-297 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takakura, A. et al.: "Establishment of an Enzyme-Linked Immunosorbent Assay for Detection of Hantavirus Antibody of Rats Using a Recombinant of Nucleocapsid Protein Expressed in Escherichia coli"Exp. Anim.. 52(1). 25-30 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Araki, K. et al.: "Truncated Hantavirus Nucleocapsid Proteins for Serotyping Hantaan,seoul,and Dobrava Hantavirus Infections"Journal of Clinical Microbiology. 39(7). 2397-2404 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2022-01-20  

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