Immunological study for prevention and treatment of HPV-positive cervical cancer.

预防和治疗HPV阳性宫颈癌的免疫学研究。

• 批准号: 11671597
• 负责人: YOSHIKAWA Hiroyuki
• 金额: $ 2.5万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671597/
• 关键词: Human Papillomavirus (HPV); variant; CIN; Cervical Cancer; L2; neutralizing antibody; E6; E7; ヒトパピローマウイルス(HPV); VLP; DNAワクチン; Variant

1. To see whether the expression of E6 and E7 genes is an essential finding in HPV-positive cervical carcinoma and cervical intraepithelial neoplasia (CIN), we constructed a RT-PCR assay using a pair of consensus primers in the E6 and E7 regions. The study demonstrates that E6 and E7 transcripts of HPV exist in virtually all HPV-positive cervical neoplasia specimens except for the absence of E7 transcripts in some of CINs.2. To elucidate whether HPV16 E6 variations carry an elevated risk for cervical cancer in Japanese population, we investigated the E6 sequence variation in CINs and invasive cervical cancers. HPVE6 variants representd a significant risk factor is common between Western and Japanese women despite the different distribution of each variant.3. We nasaly immunized Balb/c mice with a synthetic peptide with the 13 aa HPV 16 L2 sequences, and examined the antibodies elicited. The serum containing the IgG antibody and the vaginal wash containing the IgA antibody neutralized HPV16 pseudovirionx and HPV11 authentic virions. The results provide a basis for the development of a peptide vaccine against broad-spectrum of genital HPVs for humans.

1。查看E6和E7基因的表达是否是HPV阳性宫颈癌和宫颈上皮内肿瘤（CIN）中的重要发现，我们使用E6和E7区域中的一对共有引物构建了RT-PCR分析。该研究表明，HPV的E6和E7转录本几乎所有HPV阳性宫颈肿瘤标本都存在，除了CINS的某些CINS.2。为了阐明HPV16 E6的变化是否在日本人群中患有宫颈癌的风险升高，我们研究了CIN和浸润性宫颈癌的E6序列变化。 HPVE6变体代表西方女性和日本女性之间常见的一个重要危险因素，尽管每个变体的分布都不同。3。我们用具有13 AA HPV 16 L2序列的合成肽对BALB/C小鼠进行免疫，并检查了引起的抗体。含有IgG抗体和阴道洗涤的血清中和IgA抗体中和HPV16 Pseudovirionx和HPV11真实病毒体。结果为人类的生殖器HPV广谱提供了开发肽疫苗的基础。

项目成果

Yoshikawa, H., et al.: "Human papillomavirus infection and other risk factiors for cervial intraepithelial neoplasia in japan"Br J Cancer. 80. 621-624 (1999)

Yoshikawa, H. 等人：“日本的人乳头瘤病毒感染和宫颈上皮内瘤变的其他危险因素”Br J Cancer。

Kawana Y, Yoshikawa H, et al.: "Human papillomavirus 16 minor capsid protein L2 N-terminal region containing a common neutralizing epitope binds to the cell surface and enters the cytoplasm."J Virology. (in press).

Kawana Y、Yoshikawa H 等人：“人乳头瘤病毒 16 小衣壳蛋白 L2 N 末端区域含有共同的中和表位，与细胞表面结合并进入细胞质。”J Virology。

Nakagawa S,Yoshikawa H: "Ubiquitous presence of E6 and E7 transcripts in human papillomavirus-positive cervical carcinomas regardless of its type."J Med Virol.. 62. 251-258 (2000)

Nakakawa S、Yoshikawa H：“无论其类型如何，在人乳头瘤病毒阳性宫颈癌中都普遍存在 E6 和 E7 转录本。”J Med Virol.. 62. 251-258 (2000)

Matsumoto, K., Yoshikawa, H., et al.: "DNA vaccination of mice with plasmid expressing human papillomavirus 6 major capsid protein L1 elicits type-specific antibodies neutralizing pseudovirions constructed in vitro"J Med Virology. 60. 200-204 (2000)

Matsumoto, K.、Yoshikawa, H. 等人：“用表达人乳头瘤病毒 6 主要衣壳蛋白 L1 的质粒对小鼠进行 DNA 疫苗接种，可引发中和体外构建的假病毒粒子的类型特异性抗体”J Med Virology。

Matsumoto K,YoshikawaH: "Enhanced oncogenicitv of human papillomavirus type 16 (HPV16)variants in Japanese population."Cancer Lett.. 156. 159-165 (2000)

Matsumoto K、YoshikawaH：“日本人群中人乳头瘤病毒 16 型 (HPV16) 变种的致癌性增强。”Cancer Lett.. 156. 159-165 (2000)