Developmental research of new generation DNA vaccine against microorganism using synthesized DNA

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390145
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: YOKOHAMA CITY UNIVERSITY
• Principal Investigator: OKUDA Kenji YOKOHAMA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDECINE, PROFESSOR, 大学院・医学研究科, 教授 (40124862)
• Co-Investigator(Kenkyū-buntansha): 島田 勝 横浜市立大学, 医学部, 講師 (40301452) ; HAMAJIMA Kenji YOKOHAMA CITY UNIVERSITY, SCHOOL OF MEDECINE, ASSISTANT PROFESSOR, 医学部, 助手 (00114611)
• Project Period (FY): 2003 – 2004
• Keywords: DNA vaccine / Virus vector / pseudomonas / HIV / El deficient adeno virus / adeno 5 / 35 virus / influenza virus

Research Abstract

In this study, we studied the importance of preventive DNA vaccine and virus vector vaccine against microbe infectious diseases. We constructed three types of DNA vaccine of pseudomonas containing Opr F/I, Pcr V and Pill genes. After immunization to mice with each or the combination of DNA vaccine, the mice were challenged with D1 strain. When immunized with the combination of three vaccines, more than 90% of the mice were survived. The preventive effect was high in order of Pcr V, OprF/I and Pili. Non immunized mice died 2 days later after challenging. Therefore, the vaccines which we constructed have strong effects to prevent infection and we confirmed that Pcr V worked as strong preventive antigen.
On the other hand, to observe preventive effects against HIV-1, we developed a new DNA vector which the genes of Gag-Pal and Env were inserted into CAG promoter and an E1 deficient adeno 5/35 virus vector which the fiber of adeno virus type 5 replaced into the fiber of adeno type35. After immunization using these novel vaccines, we challenged monkeys with SHIV89.6. At the group which were immunized with DNA vaccine+Ad5/35, the viral load kept under the detectable level up to 25th weeks. Former adeno virus vector of type 5 had some faults such as liver obstacle. However, it became clear that Ad5/35 vector was best for human.
From these results, we are going to develop more convenient immunizing route of pseudomonas vaccine for clinical trial. On HIV-1, we are planning to join with some pharmaceutical companies to do phase I clinical trial. Furthermore, we hope to develop other best DNA vaccines or virus vector vaccines against severe infectious diseases such as O-157 or Ave influenza using Ad5/35 vector.

Research Products

• [Journal Article] Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector. (2005)
  • Author(s): Yokoo N et al.
  • Journal Title: Arthritis Rheum 52・1 Pages: 164-170
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Combination of DNA vaccine and adenovirus vector by cutaneous administration induced strong HIV-specific cellular immune responses in mice. (2005)
  • Author(s): Takakura M et al.
  • Journal Title: Vaccine 23・7 Pages: 847-848
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Vaccination of rhesus macaques with recombinant mycobacterium bovis calmette-guerin env V3 elicites neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif. (2005)
  • Author(s): Someya K et al.
  • Journal Title: J Virol 79・3 Pages: 1452-1462
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Comparison of antigen-specific cellurar immune responses between individual PBMCs and splenocytes (2005)
  • Author(s): Xin K-Q et al.
  • Journal Title: Vaccine 23 Pages: 2954-2955
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse model of scleroderma (2005)
  • Author(s): Shen Y et al.
  • Journal Title: J Autoimmune 24 Pages: 183-190
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The F(ab')2 fragment of an Ab-specific monoclonal antibody reduces Ab-deposits in the brain (2005)
  • Author(s): Tamura Y et al.
  • Journal Title: Neurobiol Dis (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cross reactive protection against influenza A virus by a topically applied DNA vaccine encoding M gene with adjuvant (2005)
  • Author(s): Ozaki T et al.
  • Journal Title: Viral Immunol (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector (2005)
  • Author(s): Yokoo, N., Saito, T., Uesugi, M., Kobayashi, N., Xin, K.-Q., Okuda, K., Mizukami, H., Ozawa, K., Koshino, T.
  • Journal Title: Arthritis Rheum 52 Pages: 164-170
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Combination of DNA vaccine and adenovirus vector by cutaneous administration induced strong HIV-specific cellular immune responses in mice (2005)
  • Author(s): Takakura, M., Okuda, K., Matsuda, T., Takeshita, F., Takakura, H., Ikezawa, Z, Xin, K.-Q.
  • Journal Title: Vaccine 23 Pages: 847-848
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vaccination of rhesus macaques with recombinant mycobacterium bovis calmette-guerin env V3 elicites neutralizing antibody-mediated protection against simian-human immunodeficiency virus with a homologous but not a heterologous V3 motif (2005)
  • Author(s): Someya, K., Cecilia, D., Ami, Y., Nakasone, T., Matsuo, K., Burda, S., Yamamoto, H., Yoshino, N., Kaizu, M., Ando, S., Okuda, K., Zolla-Pazner, S., Yamazaki, S., Yamamoto, N., Honda, M.
  • Journal Title: J Virol. 79 Pages: 1452-1462
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparison of antigen-specific cellurar immune responses between individual PBMCs and splenocytes (2005)
  • Author(s): Xin, K.-Q., Ohta, S., Jounai, N., Okuda, K.
  • Journal Title: Vaccine 23 Pages: 2954-2955
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse model of scleroderma (2005)
  • Author(s): Shen, Y., Ichino, M., Nakazawa, M., Ikejima, T., Kojima, Y., Okuda, K., Minami, M.
  • Journal Title: J Autoimmune 24 Pages: 183-190
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cross reactive protection against influenza A virus by a topically applied DNA vaccine encoding M gene with adjuvant (2005)
  • Author(s): Ozaki, T., Yauchi M., Xin, K.-Q., Hirahara, F., Okuda, K.
  • Journal Title: Viral Immunol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Polygene DNA vaccine induces a high level of protective effect against HIV-vaccinia virus challenge in mice. (2004)
  • Author(s): Shinoda K et al.
  • Journal Title: Vaccine 22・27-28 Pages: 3676-3690
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Improvement of DNA vaccine immunogenicity by a dual antigen expression system. (2004)
  • Author(s): Sasaki S et al.
  • Journal Title: Biochem Biophys Res Commun 315・1 Pages: 38-43
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A consecutive prime-boost vaccination of mice with simian immunodeficiency virus (SIV) gag/pol DNA and recombinant vaccinia virus DIs elicits effective anti-SIV immunity. (2004)
  • Author(s): Someya K et al.
  • Journal Title: J Virol 78・18 Pages: 9842-9853
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity. (2004)
  • Author(s): Devito C et al.
  • Journal Title: J Immunol 173・11 Pages: 7078-7089
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells. (2004)
  • Author(s): Takenouchi H et al.
  • Journal Title: J Cell Sci 117・pt17 Pages: 3911-3922
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Construction and immunogenicity study of a 297-bp humanized HIV V3 DNA of an approximated last common ancestor in mice. (2004)
  • Author(s): Sirivichayakul S et al.
  • Journal Title: Asian Pac J Allergy Iminunol 22 Pages: 49-60
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuLV pseudovirus challenge in vivo. (2004)
  • Author(s): Hinkula J et al.
  • Journal Title: Cells Tissues Organs 177・3 Pages: 169-184
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Polygene DNA vaccine induces a high level of protective effect against HIV-vaccinia virus challenge in mice (2004)
  • Author(s): Shinoda, K., Xin, K.-Q., Johna, I.N., Kojima, Y., Tamura, Y., Okada, E., Kawamoto, S., Okuda, K., Klinman, D., Okuda, K.
  • Journal Title: Vaccine 22 Pages: 3676-3690
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Improvement of DNA vaccine immunogenicity by a dual antigen expression system (2004)
  • Author(s): Sasaki, S., Takeshita, F., Oikawa, T., Kojima, Y., Xin, K.-Q., Okuda, K., Ishii, N.
  • Journal Title: Biochem Biophys Res Commun 315 Pages: 38-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] consecutive prime-boost vaccination of mice with simian immunodeficiency virus (SIV) gag/pol DNA and recombinant vaccinia virus DIs elicits effective anti-SIV immunity. A consecutive prime-boost vaccination of mice with simian immunodeficiency virus (SIV) gag/pal DNA and recombinant vaccinia virus DIs elicits effective anti-SIV immunity (2004)
  • Author(s): Someya, K., Xin K.-Q., Matsuo, K., Okuda, K., Yamamoto, N., Honda, M.
  • Journal Title: J Virol 78 Pages: 9842-9853
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity (2004)
  • Author(s): Devito, C., Zuber, B., Schroder, U., Benthin, R., Okuda, K., Broliden, K., Wahren, B., Hinkula, J.
  • Journal Title: J Immunol 173 Pages: 7078-7089
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells (2004)
  • Author(s): Takenouchi, H., Kiyokawa, N., Taguchi, T.
  • Journal Title: J Cell Sci 117 Pages: 3911-3922
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Construction and immunogenicity study of a 297-bp humanized HIV V3 DNA of an approximated last common ancestor in mice (2004)
  • Author(s): Sirivichayakul, S., Tirawatnapong, T., Ruxrungtham, K., Oelrichs, R., Lorenzen, S.L., Xin, K.-Q., Okuda, K., Phanuphak, P.
  • Journal Title: Asian Pac J Allergy Immunol. 22 Pages: 49-60
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuL V pseudovirus challenge in vivo (2004)
  • Author(s): Hinkula, J., Rollman, E., Lundholm, P., Benthin, R.M., Okuda, K., Wahren, B.
  • Journal Title: Cells Tissues Organs 177
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Adjuvant formulations and delivery systems for DNA vaccines. (2003)
  • Author(s): Sasaki S et al.
  • Journal Title: Methods 31・3 Pages: 243-254
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Immunogenicity and protective efficacy of orally administred recombinant Lactococcus lactis expressing surface-bound HIV Env. (2003)
  • Author(s): Xin K-Q et al.
  • Journal Title: Blood 177・3 Pages: 169-184
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A DNA vaccine containing inverted terminal repeats from adeno-associated virus increases immunity to HIV. (2003)
  • Author(s): Xin K-Q et al.
  • Journal Title: J Gene Med 5 Pages: 438-445
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of the rev gene to the immunogenicity of DNA vaccines targeting the envelope glycoprotein of HIV. (2003)
  • Author(s): Jounai N et al.
  • Journal Title: J Gene Med 5 Pages: 609-617
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chitin micro-paricles(CMP) : a useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine. (2003)
  • Author(s): Hamajima K et al.
  • Journal Title: Viral Immunol 16・4 Pages: 541-547
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Adjuvant formulations and delivery systems for DNA vaccines (2003)
  • Author(s): Sasaki, S., Takeshita, F., Xin, K.-Q., Ishii, N., Okuda, K.
  • Journal Title: Methods 31 Pages: 243-254
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A DNA vaccine containing inverted terminal repeats from adeno-associated virus increases immunity to HIV (2003)
  • Author(s): Xin, K.-Q., Ooki, T., Jounai, N., Mizukami, H., Hamajima, K., Kojima, Y., Ohba, K., Toda, Y,.Hirai, S., Klinman, D.M., Ozawa, K., Okuda, K.
  • Journal Title: J Gene Med 5 Pages: 438-445
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env (2003)
  • Author(s): Xin, K.-Q., Hoshino, Y., Toda, Y., Igimi, S., Kojima, Y., Jounai, N., Ohba, K., Kushiro, A., Kiwaki, M., Hamajima, K., Klinman, D., Okuda, K.
  • Journal Title: Blood 102 Pages: 223-228
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of the rev gene to the immunogenicity of DNA vaccines targetting the envelope glycoprotein of HIV (2003)
  • Author(s): Jounai, N., Okuda, K., Kojima, Y., Toda, Y., Hamajima, K., Ohba, K., Klinman, D., Xin, K.-Q.
  • Journal Title: J Gene Med 5 Pages: 609-617
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chitin micro-particles (CMP) is a useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine (2003)
  • Author(s): Hamajima, K., Kojima, Y., Matsui, K., Toda, Y., Jounai, N., Ozaki, T., Xin, K.-Q., Strong, P., Okuda, K.
  • Journal Title: Viral Immunol 16 Pages: 541-547
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Handbook of Proteolytic Enzymes 2^<nd> Edition (Edited by Barret, A.J., Rawlings, N.D., and Woessner J.F) (2004)
  • Author(s): Fukushima J., Okuda K.
  • Total Pages: 2140
  • Publisher: Elsevier Ltd.
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] キメラ5型/35型アデノウイルスベクター (2004)
  • Inventor(s): 奥田 研爾
  • Industrial Property Rights Holder: (株)プライミューン, 日本医薬品工業(株)
  • Industrial Property Number: PCT/JP2004/017375(国際特許)
  • Filing Date: 2004-11-24
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] 抗ヒト免疫不全ウイルス感染防御用キメラ5型/35型アデノウイルスベクター (2003)
  • Inventor(s): 奥田 研爾
  • Industrial Property Rights Holder: (株)プライミューン, 日本医薬品工業(株)
  • Industrial Property Number: 特願2003-399016
  • Filing Date: 2003-11-28
  • Description: 「研究成果報告書概要(和文)」より