Induction of protective immunity against malaria by MSP1/hsc70 fusion protein vaccine

• Project/Area Number: 12670234
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 寄生虫学(含医用動物学)
• Research Institution: Nagasaki University
• Principal Investigator: YUI Katsuyuki Nagasaki University, Molecular Medicine, Professor, 医学部, 教授 (90274638)
• Co-Investigator(Kenkyū-buntansha): UDONO Heiichiro Nagasaki University, Molecular Medicine, Associate Professor, 医学部, 助教授 (50260659)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,900,000); Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: Malaria / vaccine / immunity / MSP1 / stress protein / adjuvant / Protozoa / infection / アジュバント / 抗体 / 抗原 / 防御

Research Abstract

We have developed a method to induce CD4 and CDS specific immune responses by immunizing mice with a particular antigen as a fusion partner of mouse heat-shock cognate protein 70 (hsc70). We used this strategy to induce protective immunity against malaria sporozoite infection. We generated a recombinant protein of MSP1 fused to hsc70 (MSP1/hsc70) and studied whether it could induce protective immunity against liver stage P. yoelii, since we found that MSP1 is expressed during liver stage of P. yoelii life cycle. The immunization of mice with MSP1/hsc70 without any additional adjuvant induced strong specific antibody responses and IFN-y production. When the immunized mice were challenged with P. yoelii sporozoites, the onset of parasitemia delayed a few days when compared with naive mice or mice immunized with hsc70 alone, suggesting the induction of protective immune responses against liver stage malaria. To confirm the MSP1-specific protective immune responses against exoerythrocytic forms of malaria infection, we performed RT-PCR analysis of P. yoelii-specific rRNA in the infected liver. The level of P. yoelii was reduced in mice immunized with this fusion protein, but not in mice immunized with hsc70 alone, suggesting that MSP1-specific protective immunity is effective at liver stage malaria. This protective immunity was transferred into naive mice by spleen cells or liver lymphocytes of immune mice but not by antiserum, indicating that the protection is mediated by cellular mechanisms. Finally, the vaccine-induced protection was observed in C57BL/6, A/J, BALB/c and C3H mice suggesting that MSP1-specific protective immunity at the exoerythrocytic stage can be induced in animals over a wide range of genetic backgrounds.

Research Products

• [Publications] I.Sano et al.: "Prolonged survival of rat cardiac allograft by proinflamatory cytokine inhibitor"J. Heart and Lung Transpl.. 20(5). 583-589 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] H.Udono et al.: "Generation of cytotoxic T lymphocytes by MHC class I ligand fused to heat shock cognate protein 70"International Immunol.. 13(10). 1233-1242 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] S.Murata et al.: "Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β"EMBOJ. 20(21). 5898-5907 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sano I., Takahashi T., Koji ., Udono H., Yui K., Ayabe H.: "Prolonged survival of rat cardiac allograft with proinflammatory cytokine inhibitor"J. Heart Lung Transplant.. 20 (5). 538-589 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Udono, H., T. Yamano, Y., Kawabata, M., Uedaj and K. Yui.: "Generation of cytotoxic T lymphocytes by MHC class I ligand fused to heat shock cognate protein 70"International Immunol.. 13 (10). 1233-1242 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Murata, S., H. Udono, N. Takahashi, N. Hamada, K. Watanabe, K. Adachi, T. Yamano, K. Yui, N. kobayashi, M. kasahara, K. Tanaka, and T. Chiba: "Immunoproteasome assembly and antigen presentation in mice lacking both PA28αand PA28β"EMBO J.. 20 (21). 5898-5907 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] I.Sano et al.: "Prolonged survival of rat cardiac allograft by proinflamatory cytokine inhibitor"J.Heart and Lung Transpl.. 20(5). 583-589 (2001)
• [Publications] H.Udono et al.: "Generation of cytotoxic T lymphocytes by MHC class I ligand fused to heat shock cognate protein 70."International Immunol.. 13(10). 1233-1242 (2001)
• [Publications] S.Murata et al.: "Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β"EMBO J.. 20(21). 5898-5907 (2001)
• [Publications] I.Sano et al.: "Prolonged survival of rat cardiac allograft by proinflamatory cytokine inhibitor"J.Heart and lung Transpl.. (In Press). (2001)