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Prophylactic and therapeutic HPV16 vaccine using yeast expressing chimeric L1 and E7 protein.

使用表达嵌合 L1 和 E7 蛋白的酵母来预防和治疗 HPV16 疫苗。

基本信息

批准号：
15591735
负责人：
SASAGAWA Toshiyuki
金额：
$ 2.3万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

High-risk HPV, such as HPV type 16 was the most important etiologic factor for cervical cancer, which is the secondary many cancer in women worldwide. Therefore, HPV vaccine development is one of the best ways to reduce the incidence of cervical cancer, especially in manu developing countries Koutsky et al. first demonstrate that HPV16-L1 virus-like particles (VLP), which was produced from yeast can protect HPV16-infection in women who undertook parenteral vaccination of the VLP. This suggests that VLP vaccine is highly effective against HPV16 infection. However, the parenteral VLP vaccine may be not useful in many developing countries, since it is very expensive and the injection procedure may be difficult to perform in such countries where medical stuffs are limited. We have found that an edible freeze-dried yeast vaccine containing HPV16-L1 protein enhanced with intranasal administration of a suboptimal dose of HPV16-VLP is able to induce HPV16-specific antibody responses in mice mo … More del system. In the present study, we tried to make recombinant yeast expressing L1-E7 chimeric protein in order to synthesize VLP containing oncoprotein E7. We made three different-sized L1-E7 DNA constracts which contained full-length of E7 and truncated L1 genes, and transfected them into yeast, and had got three strains of yeast expressing 57kD, 63KD, and 67KD proteins, respectively. Since we succeeded to purify VLP from the yeast producing 63KD protein, we used this strain for an edible yeast vaccine in the mice model system. If the chimeric L1-E7 VLP induced antibody against HP16, and incorporated E7 protein induced cytotoxic T lymphocytes killing HPV16-infected cell, this vaccine might be useful as prophylactic and therapeutic vaccine against HPV16 infection. In the preliminary experiment, we found that this vaccine induces HPV16 L1 antibody in the immunized mice. Now we are going to investigate this further, and to test the cytotoxic T lymphocyte response to HPV16-E7 protein in the mice Less

高危HPV，如HPV16型，是宫颈癌最重要的病因，宫颈癌是全球女性的第二大癌症。因此，开发HPV疫苗是降低宫颈癌发病率的最佳方法之一，特别是在马努发展中国家，Koutsky等人。首次证明了从酵母中产生的HPV16-L1病毒样颗粒(VLP)可以保护接受VLP非肠道接种的妇女的HPV16感染。这表明VLP疫苗对HPV16感染是高效的。然而，非肠道VLP疫苗在许多发展中国家可能没有用处，因为它非常昂贵，而且在这些医疗人员有限的国家，注射程序可能很难进行。我们已经发现，含有hpv16-l1蛋白的可食性冻干酵母疫苗，加上鼻腔注射亚最佳剂量的hpv16-vlp，能够在小鼠的mo…中诱导hpv16特异性抗体反应。更多的DELL系统。在本研究中，我们试图使重组酵母表达L1-E7嵌合蛋白，以合成含有癌蛋白E7的VLP。我们制备了三种不同大小的L1-E7 DNA，分别含有全长的E7基因和截短的L1基因，并将它们导入酵母中，获得了三株分别表达57kD、63KD和67KD蛋白的酵母菌株。由于我们成功地从产生63KD蛋白的酵母中纯化出VLP，因此我们将该菌株用于小鼠模型系统中的食用酵母疫苗。如果L1-E7嵌合VLP诱导抗HP16抗体，并结合E7蛋白诱导的细胞毒性T淋巴细胞杀伤HPV16感染细胞，该疫苗有望成为预防和治疗HPV16感染的疫苗。在初步实验中，我们发现该疫苗在免疫的小鼠中诱导产生HPV16L1抗体。现在我们将对此进行进一步的研究，并检测小鼠对HPV16-E7蛋白的细胞毒T淋巴细胞反应。

项目成果

期刊论文数量（41）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation. 412, 13-19, 2003.

G2 DNA 损伤检查点废除后，p53 的缺失会导致 M 期延迟。

DOI：
发表时间：
2003
期刊：
Arch.Biochem.and Biophysics 412
影响因子：
0
作者：
Minemoto Y;Uchida S. et al.
通讯作者：
Uchida S. et al.

Expression of Epstein-Barr virus in thyroid carcinoma correlated with tumor progression. 34, 1170-1177, 2003.

甲状腺癌中 Epstein-Barr 病毒的表达与肿瘤进展相关。

DOI：
发表时间：
2003
期刊：
Human pathology 34
影响因子：
0
作者：
Shimakage M;Kawahara K. et al.
通讯作者：
Kawahara K. et al.

Sasagawa T, Rose RC, et al.: "Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids"Int J Cancer. 104. 328-335 (2003)

Sasakawa T、Rose RC 等人：“粘膜免疫球蛋白-A 和-G 对致癌人乳头瘤病毒衣壳的反应”Int J Cancer。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.

DOI：
10.1016/s0003-9861(03)00010-9
发表时间：
2003-04
期刊：
Archives of biochemistry and biophysics
影响因子：
3.9
作者：
Y. Minemoto;Sanae Uchida;M. Ohtsubo;M. Shimura;T. Sasagawa;M. Hirata;H. Nakagama;Y. Ishizaka;K. Yamashita
通讯作者：
Y. Minemoto;Sanae Uchida;M. Ohtsubo;M. Shimura;T. Sasagawa;M. Hirata;H. Nakagama;Y. Ishizaka;K. Yamashita

特許出願

专利申请