CTL responses to vaccination in CRPV rabbit model

宫颈癌是由感染高危人乳头瘤病毒(HPV)引起的。这种癌症的病毒病因学表明，应该有可能开发出高度特异和有效的抗病毒和抗肿瘤疫苗。HPV感染和相关病变的控制被认为是通过细胞毒性T细胞(CTL)的作用而介导的。研究高危(癌症相关)乳头瘤病毒感染的唯一小动物模型是棉尾兔乳头瘤病毒(CRPV)-兔模型。使用这种模型，我的实验室已经生产了一些CRPV疫苗，这些疫苗可以保护兔子免受初级CRPV感染，或者抑制预先确定的感染的临床表现。我们超越目前体内结果的能力受到了这样一个事实的阻碍，即目前还没有针对兔子的CTL测试。由于免疫学的最新进展使建立兔CTL试验成为可能，这是我们项目的目标。我们的具体目标是：1)为CTL靶点的开发提供永生细胞来源；2)产生抗原特异性靶细胞；3)利用免疫兔子的效应细胞建立CTL检测方法。

Cervical cancer is caused by infection with high-risk human papillomaviruses (HPVs). The viral etiology of this cancer indicates that it should be possible to develop highly specific and effective antiviral and antitumor vaccines. The control of HPV infection and associated lesions is believer to be mediated through the action of cytotoxic T cells (CTLs). The only small animal model for the study of high risk (cancer-associated) papillomavirus infection is the cottontail rabbit papillomavirus (CRPV)-rabbit model. Using this model, my laboratory has produced a number of CRPV vaccines that protect rabbits against primary CRPV infection or that suppress the clinical manifestations of a preestablished infection. Our ability to advance beyond the current in vivo results is hindered by the fact that a CTL assay for rabbits is currently not available. Since recent advances in immunology make it feasible to develop a rabbit CTL assay, this is the goal of our project. Our specific aims are: 1) to produce a source of immortal cells for the development of CTL targets; 2) to generate antigen-specific target cells; 3) to develop a CTL assay using effector cells from vaccinated rabbits.