ANALYSIS OF PAPILLOMAVIRUSES

乳头瘤病毒(PV)感染动物和人的上皮细胞， 它们通常会在感染部位诱导良性增殖。 然而，恶性进展之间有很强的联系。 人类生殖器病变和某些HPV类型，最常见的是HPV16。 我们已经为HPV16和其他PV产生了病毒样颗粒(VLP) 由L1主要衣壳蛋白或L1+L2，次要衣壳蛋白组成 衣壳蛋白。探索这些试剂是否有可能 有可能成为预防PV的亚单位疫苗的基础 我们已经在动物身上进行了预防性疫苗试验 模特们。作为之前一项研究的后续研究，我们在该研究中展示了 棉尾兔(CR)PV VLP对兔皮肤的保护作用 对于传染性CRPV的挑战，我们已经在 一种粘膜模型。牛(B)PV4型VLP的系统接种 保护牛免受感染BPV4的口腔粘膜攻击。 我们已经开发了两种分析方法，这两种方法应该可以用于定量 人VLP疫苗中和抗体效价的评价 审判。一种是HPV16的体外中和试验，该试验基于 人乳头瘤病毒16型衣壳蛋白与传染性病毒的关系 BPV1基因组。第二种是VLP血凝抑制试验 在动物PV研究中，它与体外病毒有很好的相关性 中和和体内保护免受实验性感染。 兔抗猪传染性支气管炎病毒血清的活性比较 两项检测中的七种生殖器HPV类型表明， 基于VLP的疫苗在人类中引发的病毒可能是特定类型的。 我们已经获得了强有力的证据表明，我们最近开发的基于VLP的 ELISA检测过去和现在的生殖器HPV感染情况。 酶联免疫吸附试验中的血清阳性与宫颈癌风险相关，甚至 在目前生殖器HPV DNA状况不同的队列中。在一系列中 定量评估HPV16相关风险的研究 各种人类癌症的感染，我们和我们的合作者 发现HPV16病毒粒子的存在与 抗体与宫颈、外阴、肛门和(意外)食道 在横断面病例对照研究中，癌症而不是阴茎癌。 在前瞻性研究中，血清阳性与 颈部和食道的后续发展，但不是喉部 或者是口交。

Papillomaviruses (PVs) infect the epithelia of animals and man where they generally induce benign proliferation at the site of infection. However, there is a strong association between malignant progression of human genital lesions and certain HPV types, most frequently HPV16. We have generated virus-like particles (VLPs) for HPV16 and other PVs that consist of the L1 major capsid protein or L1 plus L2, the minor capsid protein. To explore the possibility that these reagents could potentially serve as the basis for a subunit vaccine to prevent PV infection, we have conducted prophylactic vaccine trials in animal models. As a follow up to a previous study in which we demonstrated that cottontail rabbit (CR)PV VLPs protected rabbits from cutaneous challenge with infectious CRPV, we have conducted a similar trial in a mucosal model. Systemic inoculation of bovine (B)PV type 4 VLPs protected cattle from oral mucosal challenge with infectious BPV4. We have developed two assays that should be useful for quantitatively evaluating neutralizing antibody titers in human VLP-based vaccine trials. One is an in vitro neutralizing assay for HPV16 that is based on infectious virus consisting of the HPV16 capsid proteins and the BPV1 genome. The second is a VLP hemagglutination inhibition assay which, in the animal PV studies, correlated well with in vitro viral neutralization and in vivo protection from experimental infection. Comparison of the activities of rabbit sera raised against VLPs of seven genital HPV types in the two assays indicated that protection elicited by VLP-based vaccines in humans is likely to be type specific. We have obtained strong evidence that our recently developed VLP-based ELISA measures past as well as current genital HPV infection. Seroprevalence in the ELISA correlated with cervical cancer risk, even in cohorts where current genital HPV DNA status did not. In a series of studies to quantitatively assess the risk associated with HPV16 infection for various human cancers, we and our collaborators have found a strong association between the presence of HPV16 virion antibodies and cervical, vulvar, anal, and (unexpectedly) esophageal cancer but not penile cancer, in cross-sectional case-control studies. In prospective studies, seropositivity was strongly associated with the subsequent development of cervical and esophageal, but not laryngeal or oral.