Genital papillomavirus (PV) infections have been recognized recently as a major public health problem. Detailed studies of pathogenesis and epidemiology of these infections will be required in order to design and implement effective control measures. It has not been possible to perform such studies previously because PV have not been propagated successfully in tissue culture, and significant quantities of well-characterized antigens have not been available. New knowledge about PV structure and the recent development of numerous procaryotic expression vectors for high level production of foreign proteins in E. coli now provide a means to produce PV antigens for use as diagnostic reagents in the study of genital PV diseases. DNA sequence analysis and monoclonal antibody studies suggest that both type specific and cross-reacting epitopes are present on papillomavirus (PV) capsid proteins. Our preliminary data suggest that many adults possess antibodies that cross-react with bovine PV. It is likely that adults also possess antibody specific for individual human PV types to which they have been exposed. Preparation of papilloma antigens that are immunoreactive and that do not carry cross-reacting epitopes would provide a means to detect specific antibodies. Large scale epidemiological studies would then become possible. In this application, we present a method for the production of type specific HPV6b capsid antigens by molecular cloning and expression in E. coli. Strategy for characterization of antigens is presented. Type-specific immunoreactive E. coli produced proteins will be used to develop a rapid screening test for the measurement of specific antibodies in human sera. Seroprevalence studies will then be done for three patient populations: patients attending a sexually transmitted diseases (STD) clinic, women attending a cervical dysplasia clinic, and college freshmen at the University of Rochester. Longitudinal testing of sera from patients enrolled in studies of interferon therapy for condyloma acuminatum will also be done in conjunction with virus typing and studies of cell-mediated immunity. These studies should define risk factors and patterns of transmission, antibody prevalence and clinical manifestations in specific populations, and the influence of immune parameters on the course of HPV 6 infection. Reactive epitopes of HPV 6 capsid protein will be defined for the first time. Studies should provide a model for investigation of other HPV types.
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