DEVELOPMENT OF VACCINES AGAINST PAPILLOMAVIRUSES

乳头瘤病毒疫苗的开发

• 批准号: 3202227
• 负责人: FELIX O WETTSTEIN
• 金额: $ 10.07万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-20 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3202227
• 关键词: Baculoviridae; Listeria; cutaneous papilloma; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; epitope mapping; humoral immunity; immunization; laboratory rabbit; lymphocyte proliferation; oncogenic virus; rabbit papillomavirus; recombinant DNA; southern blotting; structural genes; vaccinia virus; viral vaccines; virus antigen; virus protein; virus replication; western blottings

Cervical cancer is one of the most common cancers in women worldwide and it is believed that a small number of genital human papillomaviruses play an essential role in the development of these cancers. Development of vaccines to protect from infection or effective in therapy of lesions could greatly reduce morbidity and mortality caused by these viruses. Because of the narrow host range of papillomaviruses, it is not possible to develop a animal model with the human viruses. Our goal is to use cottontail rabbit papillomavirus (CRPV) as an animal model to test strategies for protective and therapeutic vaccine development. CRPV, as some of the human viruses, is associated with the development of cancers. The specific aims are: 1) Develop a unique novel system for vaccines based on the used Listeria monocytogenes and test it in the CRPV system. 2) Construct recombinant vaccinia viruses expressing both viral structural genes for optimal maintenance of conformational epitopes and expressing viral protein and IL2 for increased T cell stimulation. 3) Express viral structural proteins with recombinant bacuolovirus or in yeast for subunit vaccine development. 4) Evaluate the possibility to develop a peptide vaccine.

宫颈癌是世界范围内女性最常见的癌症之一， 据信，少数生殖器人乳头瘤病毒发挥作用， 在这些癌症的发展中发挥着至关重要的作用。 发展 预防感染或有效治疗病变的疫苗可 大大降低这些病毒引起的发病率和死亡率。 因为 乳头状瘤病毒的宿主范围狭窄，不可能发展成 一个人类病毒的动物模型。 我们的目标是利用棉尾鼠 兔乳头瘤病毒（CRPV）作为动物模型，以测试 保护性和治疗性疫苗开发。 CRPV，作为一些人类 病毒，与癌症的发展有关。 具体目标是： 1)基于所用李斯特菌开发独特的疫苗新系统 单核细胞增多症，并在CRPV系统中进行测试。 2)构建表达两种病毒结构的重组痘苗病毒 用于最佳维持构象表位和表达的基因 病毒蛋白和IL 2用于增加T细胞刺激。 3)用重组杆状病毒表达病毒结构蛋白， 用于亚单位疫苗开发的酵母。 4)评估开发肽疫苗的可能性。