ANIMAL ORAL PAPILLOMAVIRUS--MODEL FOR A VACCINE

乳头状瘤病毒在诱导恶性上皮细胞 人类口腔和生殖道的肿瘤。 在我们的第一笔赠款中 由美国国家癌症研究所授予，我们开发了一个犬模型， 用于评估疫苗在预防感染中的有效性， 嗜粘膜乳头状瘤病毒（COPV）。我们的研究结果表明， L1衣壳蛋白疫苗的全身给药完全 有效预防口腔肿瘤。此外，研究 证明了L1构象和L1型对于 诱导保护性体液（IgG）免疫。最终适用 针对人类亲粘膜病毒的L1疫苗将具有显著的 对妇女保健和保健支出的积极影响 用于检测和治疗乳头瘤病毒引起的疾病的护理系统 恶性肿瘤 在目前的拨款中，我们建议定义的分子决定因素， L1是天然构象和成功构建所需的 接种疫苗预防COPV感染。我们还建议探索L1 参与病毒体装配和类型特异性抗原性的结构域。 此外，我们还计划将犬模型扩展到 生殖器病变，以便我们可以研究宿主激素的作用 在COPV诱导的肿瘤的起始和生长中的状态。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 抗体的 总之，该提案的目标是定义分子 L1免疫原性的要求，并将犬模型扩展到 生殖器肿瘤的分析，以精确模拟生物学， 人乳头瘤病毒引起生殖器肿瘤。

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.