Preparation of peptide vaccines according to the cassette theory against newly emerged influenza virus

根据盒式理论制备新型流感病毒肽疫苗

• 批准号: 10557025
• 负责人: OGASAWARA Kazumasa
• 金额: $ 6.85万
• 依托单位: SHIGA UNIVERSITY OF MEDICAL SCIENCE (1999)Hokkaido University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557025/
• 关键词: MHC; peptide vaccine; newly emerged influenza virus; HA; cassette theory; CTL; NP; anti-CD40 antibody

1. According to the cassette theory, we prepared a synthetic peptide vaccine against H5 subtype influenza viruses. The peptide, however, could not induce neutralizing antibodies specific for H5 subtype influenza viruses in mice. This result suggests that all antibodies produced by immunizing with the peptides prepared according to the cassette theory could not recognize their original proteins. Thus, we are preparing a new peptide which can mimic the original protein. Namely, it contains a circular peptide formed with a disulfied bond and an I-AィイD1bィエD1 binding component (46F/54A).2. After inoculation with NP366-374 peptide of a H3 subtype influenza virus in multilamellar liposome and anti-CD40 monoclonal antibody into nasal cavity of mice, the H3 subtype influenza virus was challenged. The virus infection could be prevented for 2 months by CTL activated in mice that were inoculated with both materials. It seems that the NP peptide vaccine is effective in preventing other subtypes influenza viruses, because NP contains little mutation. Thus, we are protecting infection of H5 subtype influenza viruses using liposomal NP366-374 peptide and anti-CD40 monoclonal antibody.

1.根据基因盒理论，我们制备了一种抗H5亚型流感病毒的合成肽疫苗。然而，该肽不能在小鼠中诱导针对H5亚型流感病毒的特异性中和抗体。该结果表明，通过用根据盒理论制备的肽免疫产生的所有抗体不能识别其原始蛋白质。因此，我们正在制备一种新的肽，它可以模拟原始蛋白质。也就是说，它含有由二硫键形成的环状肽和I-A β D1 b β D1结合组分（46 F/54 A）。将H3亚型流感病毒NP 366 -374多肽的多层脂质体和抗CD 40单克隆抗体接种于小鼠鼻腔，攻击H3亚型流感病毒。用两种材料接种的小鼠，通过激活CTL可预防病毒感染2个月。NP肽疫苗对其他亚型流感病毒的预防效果较好，因为NP含有很少的突变。因此，我们使用脂质体NP 366 -374肽和抗-CD 40单克隆抗体保护H5亚型流感病毒的感染。

项目成果

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Namba,K：“在 H-2A^K 携带小鼠中诱导实验性自身免疫性葡萄膜视网膜炎 (EAV) 的肽的鉴定”Clin.Exp.Immunol.111。

Ogasawara, K: "Synthetic peptide vaccines effective in preventing virus infection"Microbiology and Immunology. 43. 915-923 (1999)

小笠原 K：“有效预防病毒感染的合成肽疫苗”微生物学和免疫学。

小笠原 一誠: "ペプチドワクチン" 治療学. 32. 1524-1528 (1998)

小笠原一政：“肽疫苗”治疗学。 32. 1524-1528 (1998)

Iwabuchi,C: "Intrathymic selection of NK1・1^+α/βT cell antigen receptor(TCR)^+ cells in transgenic mice Learing TCR specific for chicken ovalbuminand restricted to I-A^α" Proc.Natl.Acad.Sci.USA. 95. 8199-8204 (1998)

Iwabuchi,C：“转基因小鼠中 NK1·1^+α/βT 细胞抗原受体 (TCR)^+ 细胞的胸腺内选择，学习对鸡卵白蛋白具有特异性的 TCR，并仅限于 I-A^α”Proc.Natl.Acad.Sci.USA。 95.8199-8204（1998）

Matsuki, N: "Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory"Vaccines. 17. 1161-1168 (1999)

Matsuki, N：“通过根据盒式理论制备的肽疫苗预防人类模型 DQ6 小鼠感染流感病毒”疫苗。