PROTECTIVE AND THERAPEUTIC IMMUNITY TO PAPILLOMATOSIS

人乳头瘤病毒（HPV）与肿瘤的发展密切相关。 宫颈癌和其他肛门生殖器癌的发病率。 治疗 癌前病变并不是对所有患者都有效。 自发 退化是常见的，但不是普遍的，可能不会发生多年。 已经报道了对许多HPV蛋白的免疫活性。 因此 接种HPV疫苗有望预防癌前病变， 发展、诱导或加速它们的退化。 疫苗 开发不能依赖于临床实验，因为 识别HPV阴性受试者的困难，因为 过多的HPV类型，并且由于癌前病变的复发， HPV再感染很常见。 此外，也不可能 在携带HPV动物中诱发疾病。 HPV的最佳动物模型 发展为癌症的疾病是棉尾兔乳头状瘤病毒 （CRPV）感染实验室家兔。 我们建议使用CRPV 开发PV疫苗的模式。初步实验将确定CRPV 编码蛋白质的基因，这些蛋白质可以引发免疫力， 乳头状瘤形成或诱导乳头状瘤消退。 后续 实验将评估相应HPV基因的能力， 在重组CRPV病毒中表达，以引起保护性或 治疗性免疫一旦发现有效的PV疫苗， 价值尽可能直接抗癌疫苗可以测试使用， 例如，由CRPV或CRPV/HPV诱导的可移植兔癌 重组体作为模型靶。

Human papillomaviruses (HPVs) are strongly implicated in the development of cervical carcinoma and other anogenital cancers. Treatment of precancerous lesions is not effective in all patients. Spontaneous regression is common but not universal, and may not occur for years. Immune activity to a number of HPV proteins has been reported. Therefore vaccination to HPV holds promise for preventing precancerous lesions from developing or inducing or accelerating their regression. Vaccine development cannot rely initially on clinical experimentation because of the difficulties in identifying HPV-negative subjects because of the plethora of HPV types, and because recurrence of precancerous lesions and HPV reinfection are common. In addition, it has been impossible to induce disease in animals with HPVs. The best animal model for HPV disease that progresses to cancer is cottontail rabbit papillomavirus (CRPV) infection of laboratory rabbits. We propose to utilize the CRPV model to develop PV vaccines. Initial experiments will identify CRPV genes coding for proteins that elicit immunity which protects against papilloma formation or induces papilloma regression. Subsequent experiments will evaluate the ability of corresponding HPV genes, expressed in recombinant CRPV viruses, to elicit protective or therapeutic immunity. Once effective PV vaccines are identified, their value as possible direct anti-cancer vaccines can be tested using, for example, transplantable rabbit carcinomas induced by CRPV or CRPV/HPV recombinants as model targets.