ANTI-IDIOTYPIC ANTIBODY VACCINES FOR HPV INFECTION

人乳头瘤病毒（HPV）基因产物存在于大多数宫颈和宫颈上皮中， 肛门生殖器癌 这些病毒引起的早期病变 已经显示在某些个体中进展为癌， 表明某些HPV类型在发展中发挥作用， 这些肿瘤。 因此，预防HPV感染的疫苗 可降低宫颈癌和肛门生殖器癌的发病率。 这样的 目前还没有疫苗。 我们的长期目标是发展单克隆抗独特型抗体 （抗Ids），其抗原性地模拟HPV上的中和表位， 其刺激针对HPV感染的宿主保护性应答。 的 具体目标是使用单克隆抗体组， HPV 11型（HPV-11）和棉尾兔乳头瘤病毒（CRPV）作为 抗原以开发一组单克隆抗Ids。 这些单克隆 抗Ids将作为（i）兔和小鼠中的免疫原进行测试， 诱导病毒中和抗体，和（ii）作为探针， 检测病毒感染者的中和抗体， 家兔 我们将使用两种乳头瘤病毒动物模型系统进行这些研究。 人乳头瘤病毒11型感染的裸鼠异种移植系统 包皮组织将被用作人类生殖器感染的模型 乳头瘤病毒型。 CRPV/家兔系统将用作 动物模型，其允许受控免疫和有意的 病毒攻击;这两种方法在异种移植系统中都不可能。 两种乳头瘤病毒模型将提供互补的阳性和阴性结果。 非交叉反应中和形式的阴性对照试剂 和针对每种病毒系统的抗Id单克隆抗体。 这是因为 这两种病毒的感染性是宿主特异性的， 通过抗体检测的中和表位是病毒特异性的。

Human papillomavirus (HPV) gene products are present in most cervical and many anogenital carcinomas. The early lesions caused by these viruses have been shown to progress to carcinomas in some individuals, which demonstrates that certain HPV types play a role in the development of these tumors. A vaccine for protection against HPV infection therefore may decrease the incidence of cervical and anogenital cancers. Such a vaccine is currently unavailable. Our long-term goal is to develop monoclonal anti-idiotypic antibodies (anti-Ids) that antigenically mimic neutralizing epitopes on HPVs and which stimulate a host protective response against HPV infection. The Specific Aims are to use sets of monoclonal antibodies which neutralize HPV type 11 (HPV-11) and cottontail rabbit papillomavirus (CRPV) as antigen to develop a panel of monoclonal anti-Ids. These monoclonal anti-Ids will be tested as (i) immunogens in rabbits and mice for the induction of virus-neutralizing antibodies, and (ii) as probes for the detection of neutralizing antibodies in virus-infected humans and rabbits. We will use two papillomavirus animal model systems for these studies. The athymic mouse xenograft system utilizing HPV-11 infected human foreskin tissue will be used as a model for infection by a human genital papillomavirus type. The CRPV/domestic rabbit system will be used as an animal model which allows for controlled immunizations and deliberate viral challenge; neither of which are possible in the xenograft system. The two papillomavirus models will provide complementary positive and negative control reagents in the form of non-cross-reactive neutralizing and anti-Id monoclonal antibodies for each viral system. This is because these two viruses are host specific in their infectivity, and because the neutralizing epitopes as detected by antibodies are virus-specific.