• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of Vaccine for Preventing HTLV-I and HIV Infection and Disease Development Using Vaccinie Virus Vector

Research Project

Project/Area Number 01870022
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionKyoto University

Principal Investigator

SHIDA Hisatoshi  Inst, for Virus Res. Kyoto Univ. Associate Professor, ウイルス研究所, 助教授 (00144395)

Co-Investigator(Kenkyū-buntansha) KANNAGI Mari  Medical School Kumamoto Univ. Assistant Professor, 医学部, 助手 (80202034)
TANAKA Yuetsu  Hygenic Sci. Kitasato Univ. Assistant Professor, 衛生学部, 助手 (30163588)
INOKO Hidetoshi  Medical School Tokai Univ. Associate Professor, 医学部, 助教授 (10101932)
SHIKU Hiroshi  Medical School Nagasaki Univ. Professor, 医学部, 教授 (80154194)
HAYAMI Masanori  Inst. for Virus Res. Kyoto Univ. Professor, ウイルス研究所, 教授 (40072946)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥32,200,000 (Direct Cost: ¥32,200,000)
Fiscal Year 1991: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1990: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1989: ¥12,200,000 (Direct Cost: ¥12,200,000)
KeywordsHTLV-I / Vaccine Vector / Vaccine / HAM / CTL / SIV / HTLV-I / ATL / AIDS / 組換えワクシニア / HIV / キラ-T細胞 / ヘルパ-T細胞
Research Abstract

(1) We examined whether there is deference between CTL activities of healthy carriers and that of ATL or HAM patients. It has been found that the HAM patients had CTL against Tax protein whereas the healthy carriers did not. Epitope mapping using synthesized peptides revealed the antigenicity of amino terminal of Tax. These CTLs were restricted by HLAA2. Measurement of. priming of T cells revealed that among healthy carriers some had primed T cel-is to pX proteins (Tax, Rex, and p2l^X) and the other did not. These high responses correlated to the HLA types characteristic to HAM patients. The primed T cells had CD8 antigen. These results suggest the relationship between anti Tax CTL and HAM.
(2) To identify the neutralization epitope of HTLV-I, anti env MAbs which had the neutralizing activity were produced. Epitope mapping using synthetic peptides revealed the gp46 amino acid sequence 191-196 as the binding site of the MAb. Immunization of the rabbits by this peptide elicited neutralizing antibody and prevented HTLV-I infection.
(3) To construct more efficient RW vectors, we introduced mutations into the region of p7.5 promoter and then placed them in tandemly repeated position. Furthermore we combined them with ATI promoter to produce stronger promoter. When we measure its efficacy by expression of CAT gene as a reporter, CAT protein was synthesized whose amount was approximately 5% of that of total cell proteins.
(4) We constructed the RW which harbors the SIV env gene under the control of ATI hybrid promoter. After cynomologous monkeys were immunized with this RVV, they were challenged by SIV to examine its capability of preventing infection. All three monkeys challenged were infected by SIV. In the second experiment, partially-purified env protein was injected as booster after the immunization by the RW, and then the monkeys were challenged by SIV. One of three monkeys immunized was protected.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Y.Tanaka.: "Immunogenecity of human T-cell leukemia virus type-I(HTLV-I)antigens for cytotoxic T lymphocytes in rat system." J.Immunol.147. 3646-3652 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Kannagi.: "Predominant recognition of human T cell leukemia virus type I(HTLV-I) pX gene products by human CD8^+ cytotoxic T cells directed against HTLV-I-infected cells." Inter.Immunol.3. 761-767 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Kannagi.: "Target epitope in the tax protein of human T cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells." J.Virol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Noguchi: "Rat cytotoxic T lymphocytes against human T lymphotropic virus type I-infected cell recognize gag and env gene encoded antigens." J.Immunol.143. 3737-3742 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N.Yoshimura.: "Simian T-cell leukemia virus type-I specific killer T-cells in naturally infected African green monkey carriers." J.Immunol.144. 2173-2178 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J.Kira.: "Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study." Ann Neurol.29. 194-201 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Shida.: "Subcellular Biochem." J.R.Harris, 36 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Tanaka: "Immunogenecity of human T-cell leukemia virus type-I (HTLV-I) antigens for cytotoxic T lymphocytes in rat system." J. Immunol. 147. 3646-3652 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Kannagi.: "Predominant recognition of human T cell leukemia virus type I (HIVL-I) pX gene products by human CD8^+ cytotoxic T cells directed against HTLV-I-infected cells." Inter. Immunol.3. 761-767 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Kannagi: "Target epitope in the tax protein of human T cell leukemia virus type I recognized by class I major histocom-patibility complex-restrictd cytotoxic T cells." J. Virol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Noguchi.: "Rat cytotoxic T lymphocytes against human T lymphotropic virus type I-infected cell recognize gag and envgene encoded antigens." J. Immunol.143. 3737-3742 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] N. Yoshimura.: "Simian T-cell leukemia virus type-I specific Killer T-cells in naturally infected African green monkey carriers." J. Immunol.144. 2173-2178 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J. Kira.: "Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy : a quantitative polymerase chain reaction study" Ann Neurol. 29. 194-201 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Shida: "Vaccine Virus Hemagglutinin." J. R. Harris Subcellular Biochem.15. 405-440 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Tanaka.: "Immunogenecity of human T-cell leukemia virus Type-I(HTLV-I)antigens for cytotoxic T lymphocytes in rat system." J.Immunol.147. 3646-3652 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Kannagi.: "Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX Gene products by human CD8^+ cytotoxic T cells directed against HTLV-I-infected cells." Inter.Immunol.3. 761-767 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Kannagi.: "Target epitope in the tax protein of human T cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells." J.Virol.

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Funahashi.: "Increased expression in vivo and in vitro of foreign genes directed by A-type inclusion hybrid promoter in recombinant vaccinia viruses." J.Virol. 65. 5584-5588 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Noguchi.: "Priming for vitro and in vivo anti-human T lymphotropic virus type l cellular immunity by virus-related protein reconstituted into liposome." J.Immunol.146. 3359- (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] J.Kira.: "Incrased HTLV-I proviral DNA in HTLV-I-associated myelopathy:a quantitative polymerase chain reaction study." Ann Neurol.29. 194-201 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Seki.,M.Oie.,Y.Ichihashi.and H.Shida.: "Hemadsorption and fusion inhibition activities of Hemagglutinin analyzed vaccinia virus mutants." Virology. 175. 372-384 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Tanaka.,H.Tozawa.and H.Shida.: "Recognition of human T cell leukemia virus typeーI (HTLVーI) gagーand pXーgene products by MHCーrestrcted syngeneic HTLVーI infected cells." J.Immunol. 144. 4202-4211 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Jacobson.,H.Shida.,D.E.McFarlin.,A.S.Fauci.and S.Koening.: "Demonstration of circulation HTLVーI pXーspecific CD8 cytotoxic T lymphocytes from patients with HTLVーI associated neurologic disease." Nature. 348. 245-248 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.Kannagi.,H.Shida.,et al.: "Human Tーcell leukemia virus type I (HTLVーI)ーspecific cytotoxic T cells from a patient with HTLVーI associated myeolopathy preferentially recognize cells expressing HTLVーI pX vitro."

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Funahashi.,S.Itamura.,H.Iinuma.,K.Nerome.,M.Sugimoto.and H.Shida.: "Increase expression in vivo and in vitro of foreign genes direted by Aーtype inclusion (ATI) hybrid promoters in recombinant vaccinia viruses."

    • Related Report
      1990 Annual Research Report
  • [Publications] 志田 壽利: "蛋白質核酸酵素" 共立出版, 11 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Noguchi et al.: "Rat cytotoxic T lymphocytes against T lymphotropic virus type I-infected cell recognize gag and env gene encoded antigens." J.Immunol.143. 3737-3742 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Tanaka et al.: "Recognition of human T cell leukemia virus type-I (HTLV-I)gag-and pX-gene products by MHC-restricted cytotoxic T lymphocytes induced in rats against syngenic…" J.Immunol. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Shida: "Vaccinia virus hemagglutinin(In Subcellular Biochem.Vol.15)" Plenum Publishing Inc., 405-440 (1989)

    • Related Report
      1989 Annual Research Report

URL: 

Published: 1989-04-01   Modified: 2019-02-15  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi