ANTIGENIC VARIABILITY AMONG HPVS INVOLVED IN GENITAL CAN

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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.