ANTIGENIC VARIABILITY AMONG HPVS INVOLVED IN GENITAL CAN

人乳头瘤病毒（HPV）是一个庞大且极其多样化的家族 只感染人类上皮细胞的病毒病原体。 某些 人乳头瘤病毒的类型与 肛门生殖道，尤其是子宫鳞状细胞癌 子宫颈 在美国，宫颈癌的发病率是 尤其是美洲土著和西班牙裔女性。 Studies at the 新墨西哥州大学的研究表明， 这些人群通常与HPV 16型相关，但 大约30%的病例与HPV 18、31和33型有关。 世界范围内的努力正在进行中，以调查HPV- 相关的癌症可以通过使用HPV疫苗来预防， HPV蛋白可用作免疫调节剂， HPV感染的自然史。 HPV的研究是 由于缺乏体外系统， 病毒的传播。 因此，努力 开发HPV疫苗将侧重于使用HPV编码的重组 用作免疫原的蛋白质。 然而，不知道是否不同 给定HPV类型的分离物是抗原性相同的或抗原性相同的 变量。 如果不同的HPV 16分离株抗原性变异， 例如，然后用由所述重组蛋白编码的重组蛋白免疫。 原型菌株可能无法预防其他HPV 16感染 菌株 我们已经证明了自然发生的人类 识别HPV衣壳蛋白和主要HPV的抗体 转化蛋白 这些蛋白质可能是疫苗的候选者 发展 我们建议使用聚合酶链反应（PCR） 从HPV DNA中扩增这些蛋白质编码序列的技术 存在于生殖道样本中。 这些编码序列将被表达 作为细菌重组蛋白，并将用作抗原靶标， Western免疫印迹测定。 HPV重组蛋白来源于 将测试临床菌株与人抗体的反应性， 与由原型编码的重组蛋白反应 HPV型菌株。 这样，我们就可以确定， 临床分离物在抗原性上与原型相似。

The human papillomaviruses (HPVs) are a large and extremely diverse family of viral pathogens that exclusively infect human epithelial cells. Certain types of human papillomaviruses are associated with carcinomas of the anogenital tract, most notably squamous cell carcinomas of the uterine cervix. In the United States, cervical carcinoma incidence rates are particularly high among Native American and Hispanic women. Studies at the University of New Mexico have demonstrated that cervical carcinomas in these populations are most commonly associated with HPV type 16, but that approximately 30% of cases are associated with HPV types 18, 31 and 33. Worldwide efforts are now underway to investigate the possibility that HPV- associated cancers could be prevented by the use of HPV vaccines, or the possibility that HPV proteins could be used as immune modulators to modify the natural history of established HPV infections. The study of HPVs is hindered by the lack of an in vitro system that will support the propagation of the viruses. It is likely, therefore, that efforts to develop HPV vaccines will focus on the use of HPV-encoded recombinant proteins for use as immunogens. However, it is not known whether different isolates of a given HPV type are antigenically identical or antigenically variant. If different isolates of HPV 16 were antigenically variant, for example, then immunization with recombinant proteins encoded by the prototype strain may not protect against infections with other HPV 16 strains. We have demonstrated the presence of naturally-occurring human antibodies that recognize HPV capsid proteins and the major HPV transforming protein. These proteins are likely candidates for vaccine development. We propose to use the polymerase chain reaction (PCR) technique to amplify the coding sequences for these proteins from HPV DNAs present in genital tract samples. These coding sequences will be expressed as bacterial recombinant proteins and will be used as antigen targets in Western immunoblot assays. The HPV recombinant proteins derived from the clinical strains will be tested for reactivity with human antibodies that are known to react with recombinant proteins encoded by the prototype strain of that HPV type. In this way, we will be able to determine whether the clinical isolates are antigenically similar to the prototypes.