STUDIES ON THE DEVELOPMENT OF HEMORRHAGIC FEVER WITH RENAL SYNDROME VACCINE USING RECOMBINANT BACULOVIRUS EXPRESSED PROTEIN.

使用重组杆状病毒表达蛋白开发出血热肾综合征疫苗的研究。

• 批准号: 02806056
• 负责人: ARIKAWA Jiro
• 金额: $ 1.22万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02806056/
• 关键词: Hemorrhagic fever with renal syndrome; Hantavirus; Baculovirus; Vaccine; Macrophage; Monoclonal antibody; Animal experiment; Virus infection; マクロファ-ジ; 単クロ-ン性抗体

1) All the neutralizing monoclonal antibodies to Hantaan virus envelope proteins examined so far caused antibody-dependent enhancement of infection to macrophage cell lines with subneutralizing amount of the antibodies. Thus, it seemed to be difficult to separate neutralization specific antigens for preparation of vaccine.2) Recombinant Hantaan virus envelope proteins were successfully expressed by the baculovirus expression system to prepare the viral antigens without any biological hazard from the Hantaan virus infection. The antigenic properties of the expressed and authentic viral antigens were indistinguishable from each other in the reaction patternswith a panel of monoclonal antibodies. However, the recombinant envelope protein induced apparently lowerneutralizing antibodies in mice than that induced with authentic viral antigen.3) Under the limitations described above, further effort which utilize adjuvants in the combination with the recombinant antigens will be required to get high neutralizing antibody.4) To examine the possible roles of the antibody-dependent enhancement of infection in the pathogenesis of hantavirus infection, development of animal models that mimics the symptoms of HFRS will be required in the future study.

1)迄今为止检查的所有针对汉坦病毒包膜蛋白的中和性单克隆抗体均以亚中和量的抗体引起对巨噬细胞系的抗体依赖性感染增强。因此，分离中和特异性抗原来制备疫苗似乎是困难的。2)杆状病毒表达系统成功表达了重组汉滩病毒包膜蛋白，制备了病毒抗原，没有任何汉滩病毒感染的生物危害。在与一组单克隆抗体的反应模式中，表达的病毒抗原和真实的病毒抗原的抗原特性彼此无法区分。然而，重组包膜蛋白在小鼠体内诱导的中和抗体明显低于用真实病毒抗原诱导的中和抗体。3)在上述限制下，需要进一步努力利用佐剂与重组抗原组合以获得高中和抗体。4)检查抗体依赖性感染增强在病毒发病机制中的可能作用。 汉坦病毒感染后，未来的研究将需要开发模拟 HFRS 症状的动物模型。

项目成果

MORI,F.: "Pathologi cal studies on central nervous tissues of rats infected with Rattus serotype hantauiws(SR-11strain)" Journal of Velerinary Medicine. B38. 665-672 (1991)

MORI,F.：“感染黄鼠血清型 hantauiws（SR-11 株）的大鼠中枢神经组织的病理学研究”《兽医医学杂志》。

KARIWA,H: "Dovelopment and aeplication of proteinG antibode assay for the detection of antsbody to hantavirus" Journal of Velerinary Medicine. 37. 345-354 (1992)

KARIWA,H：“用于检测蚂蚁体汉坦病毒的 ProteinG 抗体测定的开发和应用”《兽医医学杂志》。

Kariwa, H., Arikawa, J., Takashima, I. and Hashimoto, N.: "Development and application of protein G antibody assay for detection of antibody to hantavirus." Journal of Virological Methods. 37. 345-354 (1992)

Kariwa, H.、Arikawa, J.、Takashima, I. 和 Hashimoto, N.：“用于检测汉坦病毒抗体的 G 蛋白抗体测定的开发和应用。”

KAWAMURA,K: "Susceptiblity of laboratory and wild rodento to Rattus on Apodemus-type hantaviwses." Acta virologica. 35. 54-63 (1991)

KAWAMURA,K：“实验室和野生啮齿类动物对黑线姬鼠型汉塔鼠上的黄鼠的敏感性。”

Yao,J.-S.: "Antibody dependent enhancement of hantavirus infection in macrophage cell lines." Archives of Virology. 122. 107-118 (1991)

Yao，J.-S.：“巨噬细胞系中汉坦病毒感染的抗体依赖性增强。”