ANALYSIS OF PAPILLOMAVIRUSES

乳头瘤病毒（PV）感染动物和人的上皮细胞， 它们通常在感染部位诱导良性增殖。 然而，恶性进展与肿瘤的发生和发展之间 人类生殖器病变和某些HPV类型，最常见的是HPV16。 我们已经产生了HPV16和其他PV的病毒样颗粒（VLP） 由L1主要衣壳蛋白或L1加L2组成，次要衣壳蛋白 衣壳蛋白 为了探索这些试剂 可能作为预防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， 模型 作为之前一项研究的后续研究， 棉尾兔（CR）PV VLP可保护家兔免受皮肤 感染性CRPV的挑战，我们已经进行了类似的试验， 粘膜模型。 牛（B）PV 4型VLP的全身接种 保护牛免受感染性BPV4的口腔粘膜攻击。 我们已经开发了两种检测方法，应该是有用的定量 评价人VLP疫苗中的中和抗体滴度 审判 一种是HPV16的体外中和试验， 对由HPV 16衣壳蛋白和 BPV1基因组。 第二种是VLP血凝抑制试验 在动物PV研究中，与体外病毒相关性良好， 中和和体内保护免受实验感染。 兔血清抗VLP活性的比较 两种检测中的7种生殖器HPV类型表明， 在人类中由基于VLP的疫苗引起的免疫应答可能是类型特异性的。 我们已经获得了强有力的证据，我们最近开发的基于VLP的 ELISA测量过去以及当前生殖器HPV感染。 ELISA中的血清阳性率与宫颈癌风险相关， 在目前生殖器HPV DNA状态没有的队列中。 在一系列 定量评估HPV16相关风险的研究 感染各种人类癌症，我们和我们的合作者已经 发现HPV16病毒粒子的存在与 抗体和宫颈、外阴、肛门和（意外）食管 癌症，而不是阴茎癌，在横断面病例对照研究。 在前瞻性研究中，血清阳性与 颈部和食管的后续发展，但不是喉 或口服。

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.