ANIMAL ORAL PAPILLOMAVIRUS--MODEL FOR A VACCINE

乳头瘤病毒在诱发恶性上皮性病变中起关键作用 人类口腔和生殖道的肿瘤。在我们的第一笔赠款中 在国家癌症研究所的奖励下，我们开发了一种犬科动物模型 为评估疫苗在预防感染方面的效果 嗜粘性乳头瘤病毒(COPV)。我们的结果表明， 系统接种L1衣壳蛋白疫苗是完全 有效预防口腔肿瘤。此外，这些研究 论证了L1构象和L1类型对 诱导保护性体液(IgG)免疫。的最终应用 人类嗜粘性病毒的L1疫苗将有显著的 对妇女保健和卫生支出的积极影响 用于检测和治疗乳头瘤病毒感染的护理系统 恶性肿瘤。 在目前的拨款中，我们建议定义以下分子决定因素 L1是本机构象和成功构象所必需的 接种预防COPV感染的疫苗。我们还建议探索L1 参与病毒粒子组装的结构域和类型特异性抗原性。 此外，我们还计划将犬模型扩展到分析 这样我们就可以研究宿主荷尔蒙的作用 COPV诱导肿瘤发生和生长的研究现状。最后，我们 还将开发体外检测COPV和HPV感染性的技术 从而可以廉价地检测和滴定抗病毒药物 抗体。 总而言之，该提案的目标是定义分子 对L1免疫原性的要求，并将犬模型扩展到 对生殖器肿瘤进行分析，以便精确地模拟生殖器肿瘤的生物学 人乳头瘤病毒引起的生殖器肿瘤。

Papillomaviruses play a critical role in inducing malignant epithelial tumors of the oral and genital tract in humans. In our first grant awarded by the National Cancer Institute, we developed a canine model for evaluating the efficacy of vaccines in preventing infection by a mucosotropic papillomavirus (COPV). Our results indicated that the systemic administration of an L1 capsid protein vaccine was completely effective in preventing oral tumors. In addition, the studies demonstrated the critical role of L1 conformation and L1 type for inducing protective humoral (IgG) immunity. The eventual application of an L1 vaccine for human mucosotropic viruses will have a significant positive impact on women's health care and on expenditures by the health care system for detecting and treating papillomavirus-induced malignancies. In the current grant we propose to define the molecular determinants of L1 which are required for native conformation and for successful vaccination against COPV infection. We also propose to explore the L1 domains participating in virion assembly and type-specific antigenicity. In addition, we also plan to extend the canine model to the analysis of genital lesions so that we can investigate the role of host hormonal status in the initiation and growth of COPV-induced tumors. Finally, we will also develop techniques to assay COPV and HPV infectivity in-vitro so that it will be possible to inexpensively detect and titer anti-viral antibodies. In summary, the goals of this proposal are to define the molecular requirements for L1 immunogenicity and to extend the canine model to the analysis of genital tumors in order to precisely mimic the biology of human papillomavirus-induced genital neoplasia.