ANTI-IDIOTYPIC ANTIBODY VACCINES FOR HPV INFECTION

用于 HPV 感染的抗独特型抗体疫苗

• 批准号: 3200815
• 负责人: NEIL D CHRISTENSEN
• 金额: $ 12.41万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3200815
• 关键词: antiidiotype antibody; athymic mouse; disease /disorder model; enzyme linked immunosorbent assay; epitope mapping; human papillomavirus; human tissue; immunization; laboratory mouse; laboratory rabbit; monoclonal antibody; neutralizing antibody; rabbit papillomavirus; statistics /biometry; viral vaccines; virion; virus antigen; virus diseases

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.

人乳头瘤病毒 (HPV) 基因产物存在于大多数宫颈和 许多肛门生殖器癌。 这些病毒引起的早期病变 已被证明在某些个体中会进展为癌症， 表明某些 HPV 类型在 这些肿瘤。 因此，有一种疫苗可以预防 HPV 感染 可能会降低宫颈癌和肛门生殖器癌的发病率。 这样一个 目前尚无疫苗。 我们的长期目标是开发单克隆抗独特型抗体 （抗 IDS），抗原性地模仿 HPV 上的中和表位， 刺激宿主针对 HPV 感染的保护反应。 这 具体目标是使用单克隆抗体组来中和 HPV 11 型 (HPV-11) 和棉尾兔乳头瘤病毒 (CRPV) 抗原来开发一组单克隆抗 Id。 这些单克隆 抗 IDS 将作为 (i) 免疫原在兔子和小鼠中进行测试 诱导病毒中和抗体，以及（ii）作为探针 检测病毒感染人类的​​中和抗体 兔子。 我们将使用两种乳头瘤病毒动物模型系统进行这些研究。 利用 HPV-11 感染人类的​​无胸腺小鼠异种移植系统 包皮组织将用作人类生殖器感染的模型 乳头瘤病毒类型。 CRPV/家兔系统将用作 允许控制免疫和有意的动物模型 病毒挑战；这两种情况在异种移植系统中都是不可能的。 这两种乳头瘤病毒模型将提供互补的阳性和 非交叉反应中和形式的阴性对照试剂 以及每个病毒系统的抗Id单克隆抗体。 这是因为 这两种病毒的感染性具有宿主特异性，并且因为 抗体检测到的中和表位是病毒特异性的。